CoChat
Sign Up
Cited by 470Cancer, Stress, Anesthesia, and Immune ResponseVagus Nerve Stimulation ResearchNerve injury and regeneration

Nerves in cancer

Open access
Zahalka, Ali H., Frenette, Paul S.·2020·Nature Reviews Cancer
DOI 10.1038/s41568-019-0237-2PMC PMC7709871
Open this paper in CoChat — free account

Abstract

The contribution of nerves to the pathogenesis of malignancies has emerged as an important component of the tumour microenvironment. Recent studies have shown that peripheral nerves (sympathetic, parasympathetic and sensory) interact with tumour and stromal cells to promote the initiation and progression of a variety of solid and haematological malignancies. Furthermore, new evidence suggests that cancers may reactivate nerve-dependent developmental and regenerative processes to promote their growth and survival. Here we review emerging concepts and discuss the therapeutic implications of manipulating nerves and neural signalling for the prevention and treatment of cancer.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41568-019-0237-2

Cites

15 of 15 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Tumors can actively recruit nerves into the TME, which can directly promote tumor growth (tumor innervation).

    “More recently, groundbreaking research has revealed that tumors can actively recruit nerves into the TME, which can then directly promote tumor growth—a phenomenon known as “tumor innervation”.319,320”

    From Drug repurposing for cancer therapy (2024) · cites this paper as [319]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 193

  1. [2]Zahalka AH Adrenergic nerves activate an angio-metabolic switch in prostate cancer. Science 358, 321– 326, doi: 10.1126/science.aah5072 (2017). 29051371 PMC5783182 This paper shows that adrenergic nerves regulate the vasculature in the TME to promote tumour growth and cancer progression. · DOI · Paper page
  2. [3]Zhao CM Denervation suppresses gastric tumorigenesis. Sci Transl Med 6, 250ra115, doi: 10.1126/scitranslmed.3009569 (2014). PMC4374618 25143365 This paper shows that surgical transection of the vagus nerve inhibits development of gastric cancer. · DOI
  3. [4]Renz BW beta2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer. Cancer Cell, doi: 10.1016/j.ccell.2017.11.007 (2017). PMC5760435 29249692 · DOI · Paper page
  4. [6]Langley J The Autonomic Nervous System, part 1 Cambridge: Heffer W. Lewis T.(1927). The Blood Vessels of the Human Skin and Their Responses (1921).
  5. [7]Erin N, Zhao W, Bylander J, Chase G & Clawson G Capsaicin-induced inactivation of sensory neurons promotes a more aggressive gene expression phenotype in breast cancer cells. Breast Cancer Res Treat 99, 351– 364, doi: 10.1007/s10549-006-9219-7 (2006). 16583263 · DOI
  6. [8]Kappos EA Denervation leads to volume regression in breast cancer. J Plast Reconstr Aesthet Surg 71, 833– 839, doi: 10.1016/j.bjps.2018.03.012 (2018). 29653898 · DOI
  7. [9]Peterson SC Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches. Cell Stem Cell 16, 400– 412, doi: 10.1016/j.stem.2015.02.006 (2015). 25842978 PMC4387376 · DOI
  8. [10]Sinha S PanIN Neuroendocrine Cells Promote Tumorigenesis via Neuronal Cross-talk. Cancer Research 77, 1868– 1879, doi: 10.1158/0008-5472.can-16-0899 (2017). 28386018 PMC5471615 · DOI
  9. [11]Saloman JL Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer. Proc Natl Acad Sci U S A 113, 3078– 3083, doi: 10.1073/pnas.1512603113 (2016). 26929329 PMC4801275 · DOI
  10. [13]Jobert M New Treatment of Cancer. The Lancet 34, 112, doi: 10.1016/s0140-6736(02)98476-x (1840). · DOI
  11. [14]Ayala GE Cancer-related axonogenesis and neurogenesis in prostate cancer. Clin Cancer Res 14, 7593– 7603, doi: 10.1158/1078-0432.CCR-08-1164 (2008). 19047084 This study provides evidence for an increase in adrenergic nerve density in human cancer. · DOI
  12. [15]Albo D Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes. Cancer 117, 4834– 4845, doi: 10.1002/cncr.26117 (2011). 21480205 · DOI
  13. [16]Raju B, Haug SR, Ibrahim SO & Heyeraas KJ Sympathectomy decreases size and invasiveness of tongue cancer in rats. Neuroscience 149, 715– 725, doi: 10.1016/j.neuroscience.2007.07.048 (2007). 17916410 · DOI
  14. [17]Huang D Nerve fibers in breast cancer tissues indicate aggressive tumor progression. Medicine (Baltimore) 93, e172, doi: 10.1097/MD.0000000000000172 (2014). 25501061 PMC4602796 · DOI
  15. [18]Partecke LI Chronic stress increases experimental pancreatic cancer growth, reduces survival and can be antagonised by beta-adrenergic receptor blockade. Pancreatology 16, 423– 433, doi: 10.1016/j.pan.2016.03.005 (2016). 27083074 · DOI
  16. [19]Shao JX Autonomic nervous infiltration positively correlates with pathological risk grading and poor prognosis in patients with lung adenocarcinoma. Thorac Cancer 7, 588– 598, doi: 10.1111/1759-7714.12374 (2016). 27766778 PMC5193011 · DOI
  17. [20]Zoucas E, Nilsson C, Alm P & Ihse I Selective microsurgical sympathetic denervation of the rat pancreas. Eur Surg Res 28, 367– 373 (1996). 8880126
  18. [21]Hayashi A Retrograde labeling in peripheral nerve research: it is not all black and white. J Reconstr Microsurg 23, 381– 389, doi: 10.1055/s-2007-992344 (2007). 17979067 · DOI
  19. [22]Huang ZJ & Zeng H Genetic approaches to neural circuits in the mouse. Annu Rev Neurosci 36, 183– 215, doi: 10.1146/annurev-neuro-062012-170307 (2013). 23682658 · DOI · Paper page
  20. [23]Tabatai M, Booth AM & de Groat WC Morphological and electrophysiological properties of pelvic ganglion cells in the rat. Brain Res 382, 61– 70 (1986). 3768682
  21. [24]McVary KT Growth of the rat prostate gland is facilitated by the autonomic nervous system. Biol Reprod 51, 99– 107 (1994). 7918880
  22. [25]Diaz R Histological modifications of the rat prostate following transection of somatic and autonomic nerves. An Acad Bras Cienc 82, 397– 404 (2010). 20563420
  23. [26]Kamiya A Genetic manipulation of autonomic nerve fiber innervation and activity and its effect on breast cancer progression. Nat Neurosci 22, 1289– 1305, doi: 10.1038/s41593-019-0430-3 (2019). 31285612 This study developed novel tools for manipulating nerve activity in the TME. · DOI
  24. [27]Thoenen H & Tranzer JP Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-hydroxydopamine. Naunyn-Schmiedebergs Archiv für Pharmakologie und Experimentelle Pathologie 261, 271– 288, doi: 10.1007/bf00536990 (1968). 4387076 · DOI
  25. [28]Krukoff TL, Fernandez MC & Vincent DH Effects of neonatal sympathectomy with 6-hydroxydopamine or guanethidine on survival of neurons in the intermediolateral cell column of rat spinal cord. J Auton Nerv Syst 31, 119– 126 (1990). 2127052
  26. [29]de Champlain J Degeneration and regrowth of adrenergic nerve fibers in the rat peripheral tissues after 6-hydroxydopamine. Can J Physiol Pharmacol 49, 345– 355 (1971). 5124933
  27. [30]Szpunar MJ, Belcher EK, Dawes RP & Madden KS Sympathetic innervation, norepinephrine content, and norepinephrine turnover in orthotopic and spontaneous models of breast cancer. Brain, Behavior, and Immunity 53, 223– 233, doi: 10.1016/j.bbi.2015.12.014 (2016). PMC4783183 26718447 · DOI
  28. [31]Horvathova L Sympathectomy reduces tumor weight and affects expression of tumor-related genes in melanoma tissue in the mouse. Stress 19, 528– 534, doi: 10.1080/10253890.2016.1213808 (2016). 27416924 · DOI
  29. [32]Coarfa C Influence of the neural microenvironment on prostate cancer. The Prostate 78, 128– 139, doi: 10.1002/pros.23454 (2018). 29131367 PMC5836952 · DOI
  30. [33]Johnson EM Jr., Cantor E & Douglas JR Jr. Biochemical and functional evaluation of the sympathectomy produced by the administration of guanethidine to newborn rats. J Pharmacol Exp Ther 193, 503– 512 (1975). 238023
  31. [34]Madden ME & Sarras MP Jr. The pancreatic ductal system of the rat: cell diversity, ultrastructure, and innervation. Pancreas 4, 472– 485 (1989). 2762275
  32. [35]Lindsay TH A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas. Neuroscience 137, 1417– 1426, doi: 10.1016/j.neuroscience.2005.10.055 (2006). 16388907 · DOI
  33. [36]Fasanella KE, Christianson JA, Chanthaphavong RS & Davis BM Distribution and neurochemical identification of pancreatic afferents in the mouse. J Comp Neurol 509, 42– 52, doi: 10.1002/cne.21736 (2008). 18418900 PMC2677067 · DOI
  34. [37]Lau MK, Davila JA & Shaib YH Incidence and survival of pancreatic head and body and tail cancers: a population-based study in the United States. Pancreas 39, 458– 462, doi: 10.1097/MPA.0b013e3181bd6489 (2010). 19924019 · DOI
  35. [38]Bai H Inhibition of chronic pancreatitis and pancreatic intraepithelial neoplasia (PanIN) by capsaicin in LSL-KrasG12D/Pdx1-Cre mice. Carcinogenesis 32, 1689– 1696, doi: 10.1093/carcin/bgr191 (2011). 21859833 PMC3204349 · DOI
  36. [39]Makki J Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance. Clin Med Insights Pathol 8, 23– 31, doi: 10.4137/CPath.S31563 (2015). 26740749 PMC4689326 · DOI
  37. [40]Berthoud HR & Neuhuber WL Functional and chemical anatomy of the afferent vagal system. Auton Neurosci 85, 1– 17, doi: 10.1016/S1566-0702(00)00215-0 (2000). 11189015 · DOI · Paper page
  38. [41]Alm P, Liedberg G & Owman C Gastric and Pancreatic Sympathetic Denervation in the Rat. Scandinavian Journal of Gastroenterology 6, 307– 312, doi: 10.3109/00365527109181125 (1971). 5561175 · DOI
  39. [42]Partecke LI Subdiaphragmatic vagotomy promotes tumor growth and reduces survival via TNFalpha in a murine pancreatic cancer model. Oncotarget 8, 22501– 22512, doi: 10.18632/oncotarget.15019 (2017). 28160574 PMC5410240 · DOI
  40. [43]Renz BW Cholinergic Signaling via Muscarinic Receptors Directly and Indirectly Suppresses Pancreatic Tumorigenesis and Cancer Stemness. Cancer Discov 8, 1458– 1473, doi: 10.1158/2159-8290.CD-18-0046 (2018). 30185628 PMC6214763 · DOI
  41. [44]Zhu Y Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression. Immunity 47, 323– 338 e326, doi: 10.1016/j.immuni.2017.07.014 (2017). 28813661 PMC5578409 · DOI
  42. [45]Partecke LI Induction of M2-macrophages by tumour cells and tumour growth promotion by M2-macrophages: a quid pro quo in pancreatic cancer. Pancreatology 13, 508– 516, doi: 10.1016/j.pan.2013.06.010 (2013). 24075516 · DOI
  43. [46]Dicken BJ Gastric adenocarcinoma: review and considerations for future directions. Ann Surg 241, 27– 39, doi: 10.1097/01.sla.0000149300.28588.23 (2005). 15621988 PMC1356843 · DOI
  44. [47]Polli-Lopes AC, Zucoloto S, de Queirós Cunha F, da Silva Figueiredo LA & Garcia SB Myenteric denervation reduces the incidence of gastric tumors in rats. Cancer Letters 190, 45– 50, doi: 10.1016/s0304-3835(02)00584-0 (2003). 12536076 · DOI
  45. [48]Muir TC, Pollock D & Turner CJ The effects of electrical stimulation of the autonomic nerves and of drugs on the size of salivary glands and their rate of cell division. J Pharmacol Exp Ther (1975). 1185606
  46. [49]Srinivasan R & Chang WW Effect of neonatal sympathectomy on the postnatal differentiation of the submandibular gland of the rat. Cell Tissue Res 180, 99– 109 (1977). 872190
  47. [50]Lillberg K Stressful life events and risk of breast cancer in 10,808 women: a cohort study. Am J Epidemiol 157, 415– 423, doi: 10.1093/aje/kwg002 (2003). 12615606 · DOI
  48. [54]Hassan S Behavioral stress accelerates prostate cancer development in mice. J Clin Invest 123, 874– 886, doi: 10.1172/JCI63324 (2013). 23348742 PMC3561807 · DOI
  49. [55]Schuller HM, Al-Wadei HA, Ullah MF & Plummer HK 3rd. Regulation of pancreatic cancer by neuropsychological stress responses: a novel target for intervention. Carcinogenesis 33, 191– 196, doi: 10.1093/carcin/bgr251 (2012). 22072614 PMC3276326 · DOI
  50. [56]Le CP Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination. Nat Commun 7, 10634, doi: 10.1038/ncomms10634 (2016). 26925549 PMC4773495 · DOI · Paper page
  51. [58]Westphalen CB Long-lived intestinal tuft cells serve as colon cancer-initiating cells. J Clin Invest 124, 1283– 1295, doi: 10.1172/JCI73434 (2014). 24487592 PMC3934168 · DOI
  52. [59]Hayakawa Y Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling. Cancer Cell 31, 21– 34, doi: 10.1016/j.ccell.2016.11.005 (2017). 27989802 PMC5225031 · DOI
  53. [60]Hebb C & Linzell JL Innervation of the mammary gland. A histochemical study in the rabbit. The Histochemical Journal 2, 491– 505, doi: 10.1007/bf01003127 (1970). 5525789 · DOI
  54. [61]Köves K, Györgyi Z, Szabó F & Boldogkői Z Characterization of the autonomic innervation of mammary gland in lactating rats studied by retrograde transynaptic virus labeling and immunohistochemistry. Acta Physiologica Hungarica 99, 148– 158, doi: 10.1556/APhysiol.99.2012.2.8 (2012). 22849839 · DOI
  55. [62]Gerendai I Transneuronal labelling of nerve cells in the CNS of female rat from the mammary gland by viral tracing technique. Neuroscience 108, 103– 118, doi: 10.1016/s0306-4522(01)00399-2 (2001). 11738135 · DOI
  56. [63]Stanke M Target-dependent specification of the neurotransmitter phenotype: cholinergic differentiation of sympathetic neurons is mediated in vivo by gp130 signaling. Development 133, 383– 383, doi: 10.1242/dev.02247 (2005). 16319110 · DOI
  57. [64]Cole SW & Sood AK Molecular pathways: beta-adrenergic signaling in cancer. Clin Cancer Res 18, 1201– 1206, doi: 10.1158/1078-0432.CCR-11-0641 (2012). 22186256 PMC3294063 · DOI
  58. [65]Pinho S Lineage-Biased Hematopoietic Stem Cells Are Regulated by Distinct Niches. Dev Cell 44, 634– 641 e634, doi: 10.1016/j.devcel.2018.01.016 (2018). 29456137 PMC5886750 · DOI
  59. [66]Maryanovich M Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche. Nat Med, doi: 10.1038/s41591-018-0030-x (2018). PMC6095812 29736022 · DOI
  60. [67]Pinho S & Frenette PS Haematopoietic stem cell activity and interactions with the niche. Nat Rev Mol Cell Biol 20, 303– 320, doi: 10.1038/s41580-019-0103-9 (2019). 30745579 PMC6483843 · DOI
  61. [68]Hanoun M Acute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche. Cell Stem Cell 15, 365– 375, doi: 10.1016/j.stem.2014.06.020 (2014). 25017722 PMC4156919 · DOI · Paper page
  62. [69]Arranz L Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms. Nature 512, 78– 81, doi: 10.1038/nature13383 (2014). 25043017 · DOI · Paper page
  63. [71]Azevedo FA Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol 513, 532– 541, doi: 10.1002/cne.21974 (2009). 19226510 · DOI · Paper page
  64. [72]Venkataramani V Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature 573, 532– 538, doi: 10.1038/s41586-019-1564-x (2019). 31534219 · DOI · Paper page
  65. [73]Venkatesh HS Electrical and synaptic integration of glioma into neural circuits. Nature 573, 539– 545, doi: 10.1038/s41586-019-1563-y (2019). 31534222 PMC7038898 · DOI · Paper page
  66. [74]Zeng Q Synaptic proximity enables NMDAR signalling to promote brain metastasis. Nature 573, 526– 531, doi: 10.1038/s41586-019-1576-6 (2019). 31534217 PMC6837873 · DOI · Paper page
  67. [75]Li L & Hanahan D Hijacking the Neuronal NMDAR Signaling Circuit to Promote Tumor Growth and Invasion. Cell 153, 86– 100, doi: 10.1016/j.cell.2013.02.051 (2013). 23540692 · DOI
  68. [76]Fernandez-Montoya J, Avendano C & Negredo P The Glutamatergic System in Primary Somatosensory Neurons and Its Involvement in Sensory Input-Dependent Plasticity. Int J Mol Sci 19, doi: 10.3390/ijms19010069 (2017). PMC5796019 29280965 · DOI
  69. [77]Knox SM Parasympathetic stimulation improves epithelial organ regeneration. Nat Commun 4, 1494, doi: 10.1038/ncomms2493 (2013). 23422662 PMC3582394 · DOI
  70. [78]Nedvetsky PI Parasympathetic innervation regulates tubulogenesis in the developing salivary gland. Dev Cell 30, 449– 462, doi: 10.1016/j.devcel.2014.06.012 (2014). 25158854 PMC4155578 · DOI
  71. [79]Emmerson E SOX2 regulates acinar cell development in the salivary gland. Elife 6, doi: 10.7554/eLife.26620 (2017). PMC5498133 28623666 · DOI
  72. [80]De Champlain J, Malmfors T, Olson L & Sachs C Ontogenesis of peripheral adrenergic neurons in the rat: pre- and postnatal observations. Acta Physiol Scand 80, 276– 288, doi: 10.1111/j.1748-1716.1970.tb04791.x (1970). 5475346 · DOI
  73. [82]Liu Y Sexually dimorphic BDNF signaling directs sensory innervation of the mammary gland. Science 338, 1357– 1360, doi: 10.1126/science.1228258 (2012). 23224557 PMC3826154 This study showed that gland-derived neurotrophins are necessary for nerve recruitment and organogenesis. · DOI
  74. [83]Mattingly A, Finley JK & Knox SM Salivary gland development and disease. Wiley Interdiscip Rev Dev Biol 4, 573– 590, doi: 10.1002/wdev.194 (2015). 25970268 PMC9273040 · DOI
  75. [84]Levi-Montalcini R & Booker B Excessive Growth of the Sympathetic Ganglia Evoked by a Protein Isolated from Mouse Salivary Glands. Proc Natl Acad Sci U S A 46, 373– 384, doi: 10.1073/pnas.46.3.373 (1960). 16578496 PMC222844 · DOI
  76. [85]Knox SM Parasympathetic innervation maintains epithelial progenitor cells during salivary organogenesis. Science 329, 1645– 1647, doi: 10.1126/science.1192046 (2010). 20929848 PMC3376907 This study showed that parasympathetic nerves pattern gland growth and development. · DOI
  77. [86]Bloom GD, Carlsoo B, Danielsson A, Hellstrom S & Henriksson R Trophic effect of the sympathetic nervous system on the early development of the rat parotid gland: a quantitative ultrastructural study. Anat Rec 201, 645– 654, doi: 10.1002/ar.1092010409 (1981). 7340569 · DOI
  78. [87]Glebova NO & Ginty DD Heterogeneous requirement of NGF for sympathetic target innervation in vivo. J Neurosci 24, 743– 751, doi: 10.1523/JNEUROSCI.4523-03.2004 (2004). 14736860 PMC6729267 · DOI
  79. [88]Wheeler EF & Bothwell M Spatiotemporal patterns of expression of NGF and the low-affinity NGF receptor in rat embryos suggest functional roles in tissue morphogenesis and myogenesis. The Journal of Neuroscience 12, 930– 945, doi: 10.1523/jneurosci.12-03-00930.1992 (1992). 1312139 PMC6576057 · DOI
  80. [89]Riccio A, Pierchala BA, Ciarallo CL & Ginty DD An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons. Science 277, 1097– 1100, doi: 10.1126/science.277.5329.1097 (1997). 9262478 · DOI
  81. [90]Lehigh KM, West KM & Ginty DD Retrogradely Transported TrkA Endosomes Signal Locally within Dendrites to Maintain Sympathetic Neuron Synapses. Cell Rep 19, 86– 100, doi: 10.1016/j.celrep.2017.03.028 (2017). 28380365 PMC5562950 · DOI
  82. [91]Burris RE & Hebrok M Pancreatic innervation in mouse development and beta-cell regeneration. Neuroscience 150, 592– 602, doi: 10.1016/j.neuroscience.2007.09.079 (2007). 18006238 PMC2245866 · DOI
  83. [92]McCredie J, Cameron J & Shoobridge R Congenital Malformations and the Neural Crest. The Lancet 312, 761– 763, doi: 10.1016/s0140-6736(78)92649-1 (1978). 80687 · DOI
  84. [93]Cameron J & McCredie J Innervation of the undifferentiated limb bud in rabbit embryo. J Anat 134, 795– 808 (1982). 7130041 PMC1167871
  85. [94]Taylor AC Development of the innervation pattern in the limb bud of the frog. The Anatomical Record 87, 379– 413, doi: 10.1002/ar.1090870409 (1943). · DOI
  86. [95]Kumar A, Godwin JW, Gates PB, Garza-Garcia AA & Brockes JP Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate. Science 318, 772– 777, doi: 10.1126/science.1147710 (2007). 17975060 PMC2696928 This study identified neurotrophins in the regenerating limb mesenchyme that mediate axonogenesis and nerve-regulated limb patterning. · DOI
  87. [96]Boilly B, Faulkner S, Jobling P & Hondermarck H Nerve Dependence: From Regeneration to Cancer. Cancer Cell 31, 342– 354, doi: 10.1016/j.ccell.2017.02.005 (2017). 28292437 · DOI
  88. [97]Properzi G, Cordeschi G & Francavilla S Postnatal development and distribution of peptide-containing nerves in the genital system of the male rat. An immunohistochemical study. Histochemistry 97, 61– 68 (1992). 1618640
  89. [98]James JM & Mukouyama YS Neuronal action on the developing blood vessel pattern. Semin Cell Dev Biol 22, 1019– 1027, doi: 10.1016/j.semcdb.2011.09.010 (2011). 21978864 PMC3230733 · DOI
  90. [99]Rageh MA Vasculature in pre-blastema and nerve-dependent blastema stages of regenerating forelimbs of the adult newt, Notophthalmus viridescens. J Exp Zool 292, 255– 266 (2002). 11857459
  91. [100]Mitogawa K, Makanae A & Satoh A Hyperinnervation improves Xenopus laevis limb regeneration. Dev Biol 433, 276– 286, doi: 10.1016/j.ydbio.2017.10.007 (2018). 29291977 · DOI
  92. [101]Grassme KS Mechanism of Action of Secreted Newt Anterior Gradient Protein. PLoS One 11, e0154176, doi: 10.1371/journal.pone.0154176 (2016). 27100463 PMC4839744 · DOI
  93. [102]Miller TJ, Deptula PL, Buncke GM & Maan ZN Digit Tip Injuries: Current Treatment and Future Regenerative Paradigms. Stem Cells Int 2019, 9619080, doi: 10.1155/2019/9619080 (2019). 30805012 PMC6360566 · DOI
  94. [103]Takeo M Wnt activation in nail epithelium couples nail growth to digit regeneration. Nature 499, 228– 232, doi: 10.1038/nature12214 (2013). 23760480 PMC3936678 This study discovered a potential mechanism for nerve-mediated regeneration in mammals. · DOI
  95. [104]Zhang Y Activation of beta-catenin signaling programs embryonic epidermis to hair follicle fate. Development 135, 2161– 2172, doi: 10.1242/dev.017459 (2008). 18480165 PMC2516408 · DOI
  96. [105]Knosp WM Submandibular parasympathetic gangliogenesis requires sprouty-dependent Wnt signals from epithelial progenitors. Dev Cell 32, 667– 677, doi: 10.1016/j.devcel.2015.01.023 (2015). 25805134 PMC4374127 · DOI
  97. [106]Lucas D Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration. Nat Med 19, 695– 703, doi: 10.1038/nm.3155 (2013). 23644514 PMC3964478 · DOI
  98. [107]Rinkevich Y Clonal analysis reveals nerve-dependent and independent roles on mammalian hind limb tissue maintenance and regeneration. Proc Natl Acad Sci U S A 111, 9846– 9851, doi: 10.1073/pnas.1410097111 (2014). 24958860 PMC4103362 · DOI
  99. [108]Ekstrand AJ Deletion of neuropeptide Y (NPY) 2 receptor in mice results in blockage of NPY-induced angiogenesis and delayed wound healing. Proc Natl Acad Sci U S A 100, 6033– 6038, doi: 10.1073/pnas.1135965100 (2003). 12730369 PMC156321 · DOI
  100. [109]Martin P Wound Healing--Aiming for Perfect Skin Regeneration. Science 276, 75– 81, doi: 10.1126/science.276.5309.75 (1997). 9082989 · DOI
  101. [110]Griffin N, Faulkner S, Jobling P & Hondermarck H Targeting neurotrophin signaling in cancer: The renaissance. Pharmacol Res 135, 12– 17, doi: 10.1016/j.phrs.2018.07.019 (2018). 30031169 · DOI
  102. [111]Stopczynski RE Neuroplastic changes occur early in the development of pancreatic ductal adenocarcinoma. Cancer Res 74, 1718– 1727, doi: 10.1158/0008-5472.CAN-13-2050 (2014). 24448244 PMC4036226 · DOI
  103. [112]Lei Y Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer. Nat Commun 8, 15130, doi: 10.1038/ncomms15130 (2017). 28440296 PMC5414062 · DOI
  104. [113]Saloman JL Systemic Depletion of Nerve Growth Factor Inhibits Disease Progression in a Genetically Engineered Model of Pancreatic Ductal Adenocarcinoma. Pancreas 47, 856– 863, doi: 10.1097/MPA.0000000000001090 (2018). 29975347 PMC6044729 · DOI
  105. [114]Miknyoczki SJ Neurotrophins and Trk receptors in human pancreatic ductal adenocarcinoma: expression patterns and effects on in vitro invasive behavior. Int J Cancer 81, 417– 427, doi: 10.1002/(SICI)1097-0215(19990505)81:3<417::AID-IJC16>3.0.CO;2-6 (1999). 10209957 · DOI
  106. [115]Pundavela J ProNGF correlates with Gleason score and is a potential driver of nerve infiltration in prostate cancer. Am J Pathol 184, 3156– 3162, doi: 10.1016/j.ajpath.2014.08.009 (2014). 25285721 · DOI
  107. [116]Weeraratna AT, Arnold JT, George DJ, DeMarzo A & Isaacs JT Rational basis for Trk inhibition therapy for prostate cancer. Prostate 45, 140– 148 (2000). 11027413
  108. [117]Pundavela J Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer. Mol Oncol 9, 1626– 1635, doi: 10.1016/j.molonc.2015.05.001 (2015). 26009480 PMC5528785 · DOI
  109. [118]Allen JK Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF Induction. Cancer Res 78, 3233– 3242, doi: 10.1158/0008-5472.CAN-16-1701 (2018). 29661830 PMC6004256 · DOI
  110. [119]Mu P SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science 355, 84– 88, doi: 10.1126/science.aah4307 (2017). 28059768 PMC5247742 · DOI
  111. [120]Francis F Doublecortin Is a Developmentally Regulated, Microtubule-Associated Protein Expressed in Migrating and Differentiating Neurons. Neuron 23, 247– 256, doi: 10.1016/s0896-6273(00)80777-1 (1999). 10399932 · DOI
  112. [121]Schaar BT, Kinoshita K & McConnell SK Doublecortin Microtubule Affinity Is Regulated by a Balance of Kinase and Phosphatase Activity at the Leading Edge of Migrating Neurons. Neuron 41, 203– 213, doi: 10.1016/s0896-6273(03)00843-2 (2004). 14741102 · DOI
  113. [122]Mauffrey P Progenitors from the central nervous system drive neurogenesis in cancer. Nature, doi: 10.1038/s41586-019-1219-y (2019). 31092925 · DOI
  114. [123]Ayanlaja AA Distinct Features of Doublecortin as a Marker of Neuronal Migration and Its Implications in Cancer Cell Mobility. Front Mol Neurosci 10, 199, doi: 10.3389/fnmol.2017.00199 (2017). 28701917 PMC5487455 · DOI
  115. [125]Fujiwara T & Uehara Y The cytoarchitecture of the wall and the innervation pattern of the microvessels in the rat mammary gland: a scanning electron microscopic observation. Am J Anat 170, 39– 54, doi: 10.1002/aja.1001700104 (1984). 6731339 · DOI
  116. [126]Kepper M & Keast J Immunohistochemical Properties and Spinal Connections of Pelvic Autonomic Neurons That Innervate the Rat Prostate-Gland. Cell and Tissue Research 281, 533– 542 (1995). 7553772
  117. [127]Folkman J, Watson K, Ingber D & Hanahan D Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 339, 58– 61, doi: 10.1038/339058a0 (1989). 2469964 · DOI · Paper page
  118. [128]Eichmann A & Brunet I Arterial innervation in development and disease. Sci Transl Med 6, 252ps259, doi: 10.1126/scitranslmed.3008910 (2014). 25186174 · DOI
  119. [129]Carmeliet P & Tessier-Lavigne M Common mechanisms of nerve and blood vessel wiring. Nature 436, 193– 200, doi: 10.1038/nature03875 (2005). 16015319 · DOI · Paper page
  120. [130]De Bock K Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154, 651– 663, doi: 10.1016/j.cell.2013.06.037 (2013). 23911327 · DOI
  121. [131]Schoors S Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis. Cell Metab 19, 37– 48, doi: 10.1016/j.cmet.2013.11.008 (2014). 24332967 · DOI
  122. [132]Felten DL & Felten SY Sympathetic noradrenergic innervation of immune organs. Brain Behav Immun 2, 293– 300 (1988). 3076478
  123. [133]McHale NG & Thornbury KD Sympathetic stimulation causes increased output of lymphocytes from the popliteal node in anaesthetized sheep. Exp Physiol 75, 847– 850 (1990). 2271162
  124. [134]Rosas-Ballina M Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334, 98– 101, doi: 10.1126/science.1209985 (2011). 21921156 PMC4548937 This study showed that the autonomic nervous system can directly regulate the immune system. · DOI · Paper page
  125. [136]Salmon H, Remark R, Gnjatic S & Merad M Host tissue determinants of tumour immunity. Nat Rev Cancer, doi: 10.1038/s41568-019-0125-9 (2019). PMC7787168 30867580 · DOI
  126. [139]Shahzad MM Stress effects on FosB- and interleukin-8 (IL8)-driven ovarian cancer growth and metastasis. J Biol Chem 285, 35462– 35470, doi: 10.1074/jbc.M110.109579 (2010). 20826776 PMC2975170 · DOI
  127. [141]Miller AM CD4+CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol 177, 7398– 7405, doi: 10.4049/jimmunol.177.10.7398 (2006). 17082659 · DOI
  128. [142]Bronte V Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers. J Exp Med 201, 1257– 1268, doi: 10.1084/jem.20042028 (2005). 15824085 PMC2213151 · DOI
  129. [143]Nakai A, Hayano Y, Furuta F, Noda M & Suzuki K Control of lymphocyte egress from lymph nodes through beta2-adrenergic receptors. J Exp Med 211, 2583– 2598, doi: 10.1084/jem.20141132 (2014). 25422496 PMC4267238 · DOI
  130. [144]Qiao G beta-Adrenergic signaling blocks murine CD8(+) T-cell metabolic reprogramming during activation: a mechanism for immunosuppression by adrenergic stress. Cancer Immunol Immunother 68, 11– 22, doi: 10.1007/s00262-018-2243-8 (2019). 30229289 PMC6326964 · DOI
  131. [145]Wong CHY, Jenne CN, Lee WY, Leger C & Kubes P Functional Innervation of Hepatic iNKT Cells Is Immunosuppressive Following Stroke. Science 334, 101– 105, doi: 10.1126/science.1210301 (2011). 21921158 · DOI
  132. [146]Mohammadpour H beta2 adrenergic receptor-mediated signaling regulates the immunosuppressive potential of myeloid-derived suppressor cells. The Journal of clinical investigation, doi: 10.1172/JCI129502 (2019). PMC6877316 31566578 · DOI
  133. [148]Borovikova LV Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458– 462, doi: 10.1038/35013070 (2000). 10839541 · DOI · Paper page
  134. [149]Cheng Y Depression-Induced Neuropeptide Y Secretion Promotes Prostate Cancer Growth by Recruiting Myeloid Cells. Clin Cancer Res 25, 2621– 2632, doi: 10.1158/1078-0432.CCR-18-2912 (2019). 30504424 · DOI
  135. [150]Joyce JA & Fearon DT T cell exclusion, immune privilege, and the tumor microenvironment. Science 348, 74– 80, doi: 10.1126/science.aaa6204 (2015). 25838376 · DOI
  136. [151]Hisasue S Cavernous nerve reconstruction with a biodegradable conduit graft and collagen sponge in the rat. J Urol 173, 286– 291, doi: 10.1097/01.ju.0000141578.84536.80 (2005). 15592098 · DOI
  137. [152]Twardowski T, Fertala A, Orgel J & San Antonio J Type I Collagen and Collagen Mimetics as Angiogenesis Promoting Superpolymers. Current Pharmaceutical Design 13, 3608– 3621, doi: 10.2174/138161207782794176 (2007). 18220798 · DOI
  138. [153]Tuxhorn JA Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling. Clin Cancer Res 8, 2912– 2923 (2002). 12231536
  139. [154]Burns-Cox N, Avery NC, Gingell JC & Bailey AJ Changes in Collagen Metabolism in Prostate Cancer: A Host Response That May Alter Progression. The Journal of Urology 166, 1698– 1701, doi: 10.1016/s0022-5347(05)65656-x (2001). 11586205 · DOI
  140. [155]Egeblad M & Werb Z New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2, 161– 174, doi: 10.1038/nrc745 (2002). 11990853 · DOI · Paper page
  141. [156]Henriksen JH, Christensen NJ & Ring-Larsen H Noradrenaline and adrenaline concentrations in various vascular beds in patients with cirrhosis Relation to haemodynamics. Clinical Physiology 1, 293– 304, doi: 10.1111/j.1475-097X.1981.tb00898.x (1981). 7199989 · DOI
  142. [157]Oben JA, Yang S, Lin H, Ono M & Diehl AM Norepinephrine and neuropeptide Y promote proliferation and collagen gene expression of hepatic myofibroblastic stellate cells. Biochemical and Biophysical Research Communications 302, 685– 690, doi: 10.1016/s0006-291x(03)00232-8 (2003). 12646223 · DOI
  143. [158]Kim-Fuchs C Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment. Brain Behav Immun 40, 40– 47, doi: 10.1016/j.bbi.2014.02.019 (2014). 24650449 PMC4102665 · DOI · Paper page
  144. [159]Szpunar MJ, Burke KA, Dawes RP, Brown EB & Madden KS The antidepressant desipramine and alpha2-adrenergic receptor activation promote breast tumor progression in association with altered collagen structure. Cancer Prev Res (Phila) 6, 1262– 1272, doi: 10.1158/1940-6207.CAPR-13-0079 (2013). 24309563 PMC3862035 · DOI
  145. [160]Chen D & Ayala GE Innervating Prostate Cancer. N Engl J Med 378, 675– 677, doi: 10.1056/NEJMcibr1714003 (2018). 29443663 · DOI
  146. [161]Lillemoe KD Chemical splanchnicectomy in patients with unresectable pancreatic cancer. A prospective randomized trial. Ann Surg 217, 447– 455; discussion 456–447 (1993). 7683868 PMC1242819 This randomized placebo-controlled trial showed that denervation improved survival in patients with cancer and elevated sensory nerve activity.
  147. [162]US National Library of Medicine. ClinicalTrials.gov, http://www.clinicaltrials.gov/ct2/show/NCT01520441, 2015). 28792816
  148. [163]Al-Wadei HA, Al-Wadei MH & Schuller HM Prevention of pancreatic cancer by the beta-blocker propranolol. Anticancer Drugs 20, 477– 482, doi: 10.1097/CAD.0b013e32832bd1e3 (2009). 19387337 PMC3366433 · DOI
  149. [164]Powe DG Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival. Oncotarget 1, 628– 638, doi: 10.18632/oncotarget.101009 (2010). 21317458 PMC3248123 · DOI
  150. [165]De Giorgi V Treatment with beta-blockers and reduced disease progression in patients with thick melanoma. Arch Intern Med 171, 779– 781, doi: 10.1001/archinternmed.2011.131 (2011). 21518948 · DOI
  151. [166]Diaz ES, Karlan BY & Li AJ Impact of beta blockers on epithelial ovarian cancer survival. Gynecol Oncol 127, 375– 378, doi: 10.1016/j.ygyno.2012.07.102 (2012). 22819786 · DOI
  152. [167]Grytli HH, Fagerland MW, Fossa SD, Tasken KA & Haheim LL Use of beta-blockers is associated with prostate cancer-specific survival in prostate cancer patients on androgen deprivation therapy. Prostate 73, 250– 260, doi: 10.1002/pros.22564 (2013). 22821802 · DOI
  153. [168]Wang HM Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy. Ann Oncol 24, 1312– 1319, doi: 10.1093/annonc/mds616 (2013). 23300016 PMC3629895 · DOI
  154. [169]Neeman E, Zmora O & Ben-Eliyahu S A new approach to reducing postsurgical cancer recurrence: perioperative targeting of catecholamines and prostaglandins. Clin Cancer Res 18, 4895– 4902, doi: 10.1158/1078-0432.CCR-12-1087 (2012). 22753587 PMC3445778 · DOI
  155. [170]Bahnson RR, Andriole GL, Clayman RV & Catalona WJ Catecholamine excess: Probable cause of postoperative tachycardia following retroperitoneal lymph node dissection (RPLND) for testicular carcinoma. Journal of Surgical Oncology 42, 132– 135, doi: 10.1002/jso.2930420213 (1989). 2796348 · DOI
  156. [171]HALME A, PEKKARINEN A & TURUNEN M ON THE EXCRETION OF NORADRENALINE, ADRENALINE, 17-HYDROXYCORTICOSTEROIDS AND 17-KETOSTEROIDS DURING THE POSTOPERATIVE STAGE. 24, S5, doi: 10.1530/acta.0.024S005 (1957). 13443797 · DOI
  157. [172]Lindenauer PK Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med 353, 349– 361, doi: 10.1056/NEJMoa041895 (2005). 16049209 · DOI
  158. [173]Blessberger H Perioperative beta-blockers for preventing surgery-related mortality and morbidity. Cochrane Database Syst Rev 3, CD004476, doi: 10.1002/14651858.CD004476.pub3 (2018). 29533470 PMC6494407 · DOI
  159. [174]Al-Niaimi A The impact of perioperative beta blocker use on patient outcomes after primary cytoreductive surgery in high-grade epithelial ovarian carcinoma. Gynecol Oncol 143, 521– 525, doi: 10.1016/j.ygyno.2016.09.019 (2016). 27693123 · DOI
  160. [175]Yap A Effect of beta-blockers on cancer recurrence and survival: a meta-analysis of epidemiological and perioperative studies. Br J Anaesth 121, 45– 57, doi: 10.1016/j.bja.2018.03.024 (2018). 29935594 · DOI
  161. [176]Musselman RP Association between perioperative beta blocker use and cancer survival following surgical resection. Eur J Surg Oncol 44, 1164– 1169, doi: 10.1016/j.ejso.2018.05.012 (2018). 29858097 · DOI
  162. [177]Cata JP Perioperative beta-blocker use and survival in lung cancer patients. J Clin Anesth 26, 106– 117, doi: 10.1016/j.jclinane.2013.10.004 (2014). 24480297 · DOI
  163. [179]Denk F, Bennett DL & McMahon SB Nerve Growth Factor and Pain Mechanisms. Annu Rev Neurosci 40, 307– 325, doi: 10.1146/annurev-neuro-072116-031121 (2017). 28441116 · DOI
  164. [180]Smith M Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1. J Clin Oncol 34, 3005– 3013, doi: 10.1200/JCO.2015.65.5597 (2016). 27400947 · DOI
  165. [181]Collins C Preclinical and clinical studies with the multi-kinase inhibitor CEP-701 as treatment for prostate cancer demonstrate the inadequacy of PSA response as a primary endpoint. Cancer Biol Ther 6, 1360– 1367, doi: 10.4161/cbt.6.9.4541 (2007). 17786033 PMC4124640 · DOI
  166. [182]Drilon A Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378, 731– 739, doi: 10.1056/NEJMoa1714448 (2018). 29466156 PMC5857389 · DOI · Paper page
  167. [183]Chan E A phase I trial of CEP-701 + gemcitabine in patients with advanced adenocarcinoma of the pancreas. Invest New Drugs 26, 241– 247, doi: 10.1007/s10637-008-9118-3 (2008). 18217204 · DOI
  168. [184]Shabbir M & Stuart R Lestaurtinib, a multitargeted tyrosine kinase inhibitor: from bench to bedside. Expert Opin Investig Drugs 19, 427– 436, doi: 10.1517/13543781003598862 (2010). 20141349 · DOI
  169. [185]US National Library of Medicine. ClinicalTrials.gov, http://www.clinicaltrials.gov/ct2/show/NCT00830180, 2014). 28792816
  170. [186]Sopata M Efficacy and safety of tanezumab in the treatment of pain from bone metastases. Pain 156, 1703– 1713, doi: 10.1097/j.pain.0000000000000211 (2015). 25919474 · DOI
  171. [187]Barford K, Keeler A, Deppmann C & Winckler B TrkA Bumps into Its Future Self. Dev Cell 42, 557– 558, doi: 10.1016/j.devcel.2017.09.002 (2017). 28950095 · DOI
  172. [188]Spitzer NC Neurotransmitter Switching? No Surprise. Neuron 86, 1131– 1144, doi: 10.1016/j.neuron.2015.05.028 (2015). 26050033 PMC4458710 · DOI
  173. [189]Habecker BA & Landis SC Noradrenergic regulation of cholinergic differentiation. Science 264, 1602– 1604, doi: 10.1126/science.8202714 (1994). 8202714 This study showed that the sympathetic neurotransmitter phenotype is plastic and mediated by the tissue-specific microenvironment. · DOI
  174. [190]Yang B, Slonimsky JD & Birren SJ A rapid switch in sympathetic neurotransmitter release properties mediated by the p75 receptor. Nat Neurosci 5, 539– 545, doi: 10.1038/nn853 (2002). 11992117 · DOI
  175. [191]Yamamori T The Cholinergic Neuronal Differentiation Factor from Heart-Cells Is Identical to Leukemia Inhibitory Factor. Science 246, 1412– 1416, doi:DOI 10.1126/science.2512641 (1989). 2512641 · DOI
  176. [192]Zurborg S Generation and characterization of an Advillin-Cre driver mouse line. Mol Pain 7, 66, doi: 10.1186/1744-8069-7-66 (2011). 21906401 PMC3185264 · DOI
  177. [193]Lau J Temporal control of gene deletion in sensory ganglia using a tamoxifen-inducible Advillin-Cre-ERT2 recombinase mouse. Mol Pain 7, 100, doi: 10.1186/1744-8069-7-100 (2011). 22188729 PMC3260248 · DOI
  178. [194]Nassar MA Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci U S A 101, 12706– 12711, doi: 10.1073/pnas.0404915101 (2004). 15314237 PMC515119 · DOI
  179. [195]Chen X A chemical-genetic approach to studying neurotrophin signaling. Neuron 46, 13– 21, doi: 10.1016/j.neuron.2005.03.009 (2005). 15820690 · DOI
  180. [196]Karai L Deletion of vanilloid receptor 1_expressing primary afferent neurons for pain control. Journal of Clinical Investigation 113, 1344– 1352, doi: 10.1172/jci20449 (2004). 15124026 PMC398431 · DOI · Paper page
  181. [197]Erin N, Boyer PJ, Bonneau RH, Clawson GA & Welch DR Capsaicin-mediated denervation of sensory neurons promotes mammary tumor metastasis to lung and heart. Anticancer Res 24, 1003– 1009 (2004). 15161056
  182. [198]Vincenzi FF Effect of botulinum toxin on autonomic nerves in a dually innervated tissue. Nature 213, 394– 395 (1967). 5339739
  183. [199]Ben-Shaanan TL Modulation of anti-tumor immunity by the brain’s reward system. Nat Commun 9, 2723, doi: 10.1038/s41467-018-05283-5 (2018). 30006573 PMC6045610 · DOI
  184. [200]Montgomery KL, Iyer SM, Christensen AJ, Deisseroth K & Delp SL Beyond the brain: Optogenetic control in the spinal cord and peripheral nervous system. Sci Transl Med 8, 337rv335, doi: 10.1126/scitranslmed.aad7577 (2016). 27147590 · DOI · Paper page
  185. [201]Sternson SM & Roth BL Chemogenetic tools to interrogate brain functions. Annu Rev Neurosci 37, 387– 407, doi: 10.1146/annurev-neuro-071013-014048 (2014). 25002280 · DOI
  186. [202]Lin CW Genetically increased cell-intrinsic excitability enhances neuronal integration into adult brain circuits. Neuron 65, 32– 39, doi: 10.1016/j.neuron.2009.12.001 (2010). 20152111 PMC2822732 · DOI
  187. [203]Amit M, Na’ara S & Gil Z Mechanisms of cancer dissemination along nerves. Nat Rev Cancer 16, 399– 408, doi: 10.1038/nrc.2016.38 (2016). 27150016 · DOI
  188. [204]Taylor HB & Norris HJ Epithelial invasion of nerves in benign diseases of the breast. Cancer 20, 2245– 2249 (1967). 6073901
  189. [205]Ali TZ & Epstein JI Perineural involvement by benign prostatic glands on needle biopsy. Am J Surg Pathol 29, 1159– 1163 (2005). 16096404
  190. [206]Cracchiolo JR Patterns of recurrence in oral tongue cancer with perineural invasion. Head Neck. 40, 1287– 1295 (2018). 29522275 PMC5980694
  191. [207]Al-Hussain T, Carter HB & Epstein JI Significance of prostate adenocarcinoma perineural invasion on biopsy in patients who are otherwise candidates for active surveillance. J Urol 186, 470– 473, doi: 10.1016/j.juro.2011.03.119 (2011). 21679997 · DOI
  192. [208]Beard CJ Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer. International Journal of Radiation Oncology*Biology*Physics 58, 19– 24, doi: 10.1016/s0360-3016(03)01433-0 (2004). 14697416 · DOI
  193. [209]Kraus RD The Perineural Invasion Paradox: Is Perineural Invasion an Independent Prognostic Indicator of Biochemical Recurrence Risk in Patients With pT2N0R0 Prostate Cancer? A Multi-Institutional Study. Adv Radiat Oncol 4, 96– 102, doi: 10.1016/j.adro.2018.09.006 (2019). 30706016 PMC6349660 · DOI

Cited by

Sorted by citations

Authors
Zahalka, A. H., & Frenette, P. S.
Affiliations
Albert Einstein College of Medicine (US)
Corresponding author
Frenette, Paul S.
ORCID
Venue
Nature Reviews Cancer
Publisher
Springer Science and Business Media LLC
Published
2020-01-23
Volume
20
Issue
3
Pages
143-157
ISSN
  • 1474-175X (ISSN-L)
  • 1474-1768
DOI
10.1038/s41568-019-0237-2
PMC
PMC7709871
OpenAlex
W3001661683
Cited by
470
References
15
Citations by year
2026: 93 · 2025: 72 · 2024: 67 · 2023: 74 · 2022: 82 · 2021: 58 · 2020: 24
FWCI
9.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature reviews. Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL097700, R01HL069438)
  • National Cancer Institute (F30CA203446)
  • National Institute of General Medical Sciences (T32GM007288)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK056638, U01DK116312)
  • National Institute of Neurological Disorders and Stroke (T32NS007098)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Keywords
peripheral nerves, tumor microenvironment, carcinogenesis, sympathetic nerves, parasympathetic nerves, sensory nerves, tumor stroma, hematologic malignancies, solid tumors, tumor progression, cancer prevention, cancer therapy
MeSH terms
Animals, Disease Susceptibility, Humans, Neoplasms, Synaptic Transmission, Neuroimmunomodulation, Signal Transduction, Autonomic Pathways, Neurotransmitter Agents, Disease Management, Tumor Microenvironment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review