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Cited by 682Cancer Cells and MetastasisTGF-β signaling in diseasesPancreatic and Hepatic Oncology Research

Cancer associated fibroblasts (CAFs) in tumor microenvironment

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Xing, Fei·2010·Frontiers in Bioscience
DOI 10.2741/3613PMC PMC2905156
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Abstract

Cancer associated fibroblasts (CAFs) is one of the most crucial components of the tumor microenvironment which promotes the growth and invasion of cancer cells by various mechanisms. CAFs demonstrate a high degree of heterogeneity due to their various origins; however, many distinct morphological features and physiological functions of CAFs have been identified. It is becoming clear that the crosstalk between the cancer cells and the CAFs plays a key role in the progression of cancer, and understanding this mutual relationship would eventually enable us to treat cancer patients by targeting CAFs. In this review, we will discuss the latest findings on the role of CAFs in tumorigenesis and metastasis as well as potential therapeutic implication of CAFs.

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  • CAFs interact with cancer cells and other cell types within the TME, playing a pivotal role in regulating tumor progression and therapeutic resistance.

    “CAFs interact with cancer cells and other cell types within the TME, playing a pivotal role in regulating tumor progression and therapeutic resistance 71.”

    From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [71]

    The Abstract and sections 5.2–5.3 describe CAF interactions with cancer cells and immune cells that promote tumor growth, invasion, and metastasis. Section 6 reports that components of a stem-cell microenvironment can promote chemotherapy resistance in acute myeloid leukemia, but it does not establish that CAFs regulate therapeutic resistance generally. Section 7 instead attributes cancer cells’ frequent resistance to therapies largely to their genomic instability. (LLM, conf=0.85)

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  1. [1]Liotta LA Kohn EC The microenvironment of the tumour-host interface Nature 2001 411 375 379 11357145
  2. [2]Rodemann HP Muller GA Characterization of human renal fibroblasts in health and disease: II. In vitro growth, differentiation, and collagen synthesis of fibroblasts from kidneys with interstitial fibrosis Am J Kidney Dis 1991 17 684 686 2042650
  3. [3]Chang HY Chi JT Dudoit S Bondre C van de Rijn M Botstein D Brown PO Diversity, topographic differentiation, and positional memory in human fibroblasts Proc Natl Acad Sci U S A 2002 99 12877 12882 12297622 PMC130553
  4. [4]Nakamura T Matsumoto K Kiritoshi A Tano Y Nakamura T Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells: in vitro analysis of tumor-stromal interactions Cancer Res 1997 57 3305 3313 9242465
  5. [5]Simian M Hirai Y Navre M Werb Z Lochter A Bissell MJ The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells Development 2001 128 3117 3131 11688561 PMC2785713
  6. [7]Hanahan D Weinberg RA The hallmarks of cancer Cell 2000 100 57 70 10647931
  7. [8]Eyden B The myofibroblast: phenotypic characterization as a prerequisite to understanding its functions in translational medicine J Cell Mol Med 2008 12 22 37 18182061 PMC3823470
  8. [9]Sappino AP Skalli O Jackson B Schurch W Gabbiani G Smooth-muscle differentiation in stromal cells of malignant and non-malignant breast tissues Int J Cancer 1988 41 707 712 2835323
  9. [10]Li H Fan X Houghton J Tumor microenvironment: the role of the tumor stroma in cancer J Cell Biochem 2007 101 805 815 17226777
  10. [11]De Wever O Demetter P Mareel M Bracke M Stromal myofibroblasts are drivers of invasive cancer growth Int J Cancer 2008 123 2229 2238 18777559
  11. [12]Garin-Chesa P Old LJ Rettig WJ Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers Proc Natl Acad Sci U S A 1990 87 7235 7239 2402505 PMC54718
  12. [13]Clement S Stouffs M Bettiol E Kampf S Krause KH Chaponnier C Jaconi M Expression and function of alpha-smooth muscle actin during embryonic-stem-cell-derived cardiomyocyte differentiation J Cell Sci 2007 120 229 238 17179203
  13. [14]Ronnov-Jessen L Petersen OW A function for filamentous alpha-smooth muscle actin: retardation of motility in fibroblasts J Cell Biol 1996 134 67 80 8698823 PMC2120928
  14. [15]Cheng JD Valianou M Canutescu AA Jaffe EK Lee HO Wang H Lai JH Bachovchin WW Weiner LM Abrogation of fibroblast activation protein enzymatic activity attenuates tumor growth Mol Cancer Ther 2005 4 351 360 15767544
  15. [16]Scanlan MJ Raj BK Calvo B Garin-Chesa P Sanz-Moncasi MP Healey JH Old LJ Rettig WJ Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers Proc Natl Acad Sci U S A 1994 91 5657 5661 7911242 PMC44055
  16. [17]Hagood JS Prabhakaran P Kumbla P Salazar L MacEwen MW Barker TH Ortiz LA Schoeb T Siegal GP Alexander CB Pardo A Selman M Loss of fibroblast Thy-1 expression correlates with lung fibrogenesis Am J Pathol 2005 167 365 379 16049324 PMC1603564
  17. [18]Koumas L Smith TJ Feldon S Blumberg N Phipps RP Thy-1 expression in human fibroblast subsets defines myofibroblastic or lipofibroblastic phenotypes Am J Pathol 2003 163 1291 1300 14507638 PMC1868289
  18. [19]Di Tommaso L Pasquinelli G Damiani S Smooth muscle cell differentiation in mammary stromo-epithelial lesions with evidence of a dual origin: stromal myofibroblasts and myoepithelial cells Histopathology 2003 42 448 456 12713621
  19. [20]Tlsty TD Stromal cells can contribute oncogenic signals Semin Cancer Biol 2001 11 97 104 11322829
  20. [21]Tsellou E Kiaris H Fibroblast independency in tumors: implications in cancer therapy Future Oncol 2008 4 427 432 18518767
  21. [22]Littlepage LE Egeblad M Werb Z Coevolution of cancer and stromal cellular responses Cancer Cell 2005 7 499 500 15950897
  22. [24]Kurose K Gilley K Matsumoto S Watson PH Zhou XP Eng C Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas Nat Genet 2002 32 355 357 12379854
  23. [25]Hill R Song Y Cardiff RD Van Dyke T Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis Cell 2005 123 1001 1011 16360031
  24. [26]Kurose K Hoshaw-Woodard S Adeyinka A Lemeshow S Watson PH Eng C Genetic model of multi-step breast carcinogenesis involving the epithelium and stroma: clues to tumour-microenvironment interactions Hum Mol Genet 2001 10 1907 1913 11555627
  25. [27]Fukino K Shen L Patocs A Mutter GL Eng C Genomic instability within tumor stroma and clinicopathological characteristics of sporadic primary invasive breast carcinoma Jama 2007 297 2103 2111 17507346
  26. [28]Pathak S Nemeth MA Multani AS Thalmann GN von Eschenbach AC Chung LW Can cancer cells transform normal host cells into malignant cells? Br J Cancer 1997 76 1134 1138 9365160 PMC2228111
  27. [29]Walter K Omura N Hong SM Griffith M Goggins M Pancreatic cancer associated fibroblasts display normal allelotypes Cancer Biol Ther 2008 7 882 888 18344687 PMC2692624
  28. [30]Allinen M Beroukhim R Cai L Brennan C Lahti-Domenici J Huang H Porter D Hu M Chin L Richardson A Schnitt S Sellers WR Polyak K Molecular characterization of the tumor microenvironment in breast cancer Cancer Cell 2004 6 17 32 15261139
  29. [31]Hay ED An overview of epithelio-mesenchymal transformation Acta Anat (Basel) 1995 154 8 20 8714286
  30. [32]Thiery JP Epithelial-mesenchymal transitions in tumour progression Nat Rev Cancer 2002 2 442 454 12189386
  31. [33]Zvaifler NJ Relevance of the stroma and epithelial-mesenchymal transition (EMT) for the rheumatic diseases Arthritis Res Ther 2006 8 210 16689999 PMC1526619
  32. [34]Forino M Torregrossa R Ceol M Murer L Della Vella M Del Prete D D'Angelo A Anglani F TGFbeta1 induces epithelial-mesenchymal transition, but not myofibroblast transdifferentiation of human kidney tubular epithelial cells in primary culture Int J Exp Pathol 2006 87 197 208 16709228 PMC2517360
  33. [35]Petersen OW Lind Nielsen H Gudjonsson T Villadsen R Ronnov-Jessen L Bissell MJ The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion Breast Cancer Res 2001 3 213 217 11434871 PMC138684
  34. [36]Oft M Akhurst RJ Balmain A Metastasis is driven by sequential elevation of H-ras and Smad2 levels Nat Cell Biol 2002 4 487 494 12105419
  35. [37]Iwano M Plieth D Danoff TM Xue C Okada H Neilson EG Evidence that fibroblasts derive from epithelium during tissue fibrosis J Clin Invest 2002 110 341 350 12163453 PMC151091
  36. [38]Petersen OW Nielsen HL Gudjonsson T Villadsen R Rank F Niebuhr E Bissell MJ Ronnov-Jessen L Epithelial to mesenchymal transition in human breast cancer can provide a nonmalignant stroma Am J Pathol 2003 162 391 402 12547698 PMC1851146
  37. [39]Direkze NC Hodivala-Dilke K Jeffery R Hunt T Poulsom R Oukrif D Alison MR Wright NA Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts Cancer Res 2004 64 8492 8495 15574751
  38. [40]Direkze NC Alison MR Bone marrow and tumour stroma: an intimate relationship Hematol Oncol 2006 24 189 195 16795113
  39. [41]Russo FP Alison MR Bigger BW Amofah E Florou A Amin F Bou-Gharios G Jeffery R Iredale JP Forbes SJ The bone marrow functionally contributes to liver fibrosis Gastroenterology 2006 130 1807 1821 16697743
  40. [42]Mishra PJ Mishra PJ Humeniuk R Medina DJ Alexe G Mesirov JP Ganesan S Glod JW Banerjee D Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells Cancer Res 2008 68 4331 4339 18519693 PMC2725025
  41. [43]Powell DW Adegboyega PA Di Mari JF Mifflin RC Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer Am J Physiol Gastrointest Liver Physiol 2005 289 G2 G7 15961883
  42. [44]Schmitt-Graff A Desmouliere A Gabbiani G Heterogeneity of myofibroblast phenotypic features: an example of fibroblastic cell plasticity Virchows Arch 1994 425 3 24 7921410
  43. [45]De Wever O Mareel M Role of tissue stroma in cancer cell invasion J Pathol 2003 200 429 447 12845611
  44. [46]Howlett AR Bissell MJ The influence of tissue microenvironment (stroma and extracellular matrix) on the development and function of mammary epithelium Epithelial Cell Biol 1993 2 79 89 8353596
  45. [47]Mahfouz SM Chevallier M Grimaud JA Distribution of the major connective matrix components of the stromal reaction in breast carcinoma. An immunohistochemical study Cell Mol Biol 1987 33 453 467 3311367
  46. [48]Dugina V Fontao L Chaponnier C Vasiliev J Gabbiani G Focal adhesion features during myofibroblastic differentiation are controlled by intracellular and extracellular factors J Cell Sci 2001 114 3285 3296 11591817
  47. [49]Singer II Kawka DW Kazazis DM Clark RA In vivo co-distribution of fibronectin and actin fibers in granulation tissue: immunofluorescence and electron microscope studies of the fibronexus at the myofibroblast surface J Cell Biol 1984 98 2091 2106 6373789 PMC2113047
  48. [50]Tlsty TD Hein PW Know thy neighbor: stromal cells can contribute oncogenic signals Curr Opin Genet Dev 2001 11 54 59 11163151
  49. [51]Zeisberg EM Tarnavski O Zeisberg M Dorfman AL McMullen JR Gustafsson E Chandraker A Yuan X Pu WT Roberts AB Neilson EG Sayegh MH Izumo S Kalluri R Endothelial-to-mesenchymal transition contributes to cardiac fibrosis Nat Med 2007 13 952 961 17660828
  50. [52]Potenta S Zeisberg E Kalluri R The role of endothelial-to-mesenchymal transition in cancer progression Br J Cancer 2008 99 1375 1379 18797460 PMC2579683
  51. [53]Zeisberg EM Potenta S Xie L Zeisberg M Kalluri R Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts Cancer Res 2007 67 10123 10128 17974953
  52. [54]Skalli O Pelte MF Peclet MC Gabbiani G Gugliotta P Bussolati G Ravazzola M Orci L Alpha-smooth muscle actin, a differentiation marker of smooth muscle cells, is present in microfilamentous bundles of pericytes J Histochem Cytochem 1989 37 315 321 2918221
  53. [55]Kuperwasser C Chavarria T Wu M Magrane G Gray JW Carey L Richardson A Weinberg RA Reconstruction of functionally normal and malignant human breast tissues in mice Proc Natl Acad Sci U S A 2004 101 4966 4971 15051869 PMC387357
  54. [56]Grum-Schwensen B Klingelhofer J Berg CH El-Naaman C Grigorian M Lukanidin E Ambartsumian N Suppression of tumor development and metastasis formation in mice lacking the S100A4(mts1) gene Cancer Res 2005 65 3772 3780 15867373
  55. [57]Goh PP Sze DM Roufogalis BD Molecular and cellular regulators of cancer angiogenesis Curr Cancer Drug Targets 2007 7 743 758 18220534
  56. [59]Li G Satyamoorthy K Meier F Berking C Bogenrieder T Herlyn M Function and regulation of melanoma-stromal fibroblast interactions: when seeds meet soil Oncogene 2003 22 3162 3171 12789292
  57. [60]Cunha GR Hayward SW Wang YZ Role of stroma in carcinogenesis of the prostate Differentiation 2002 70 473 485 12492490
  58. [61]Yuan J Glazer PM Mutagenesis induced by the tumor microenvironment Mutat Res 1998 400 439 446 9685702
  59. [62]Barcellos-Hoff MH Ravani SA Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells Cancer Res 2000 60 1254 1260 10728684
  60. [63]Barcellos-Hoff Radiation-induced transforming growth factor beta and subsequent extracellular matrix reorganization in murine mammary gland Cancer Res 1993 53 3880 3886 8358713
  61. [64]Tsushima H Kawata S Tamura S Ito N Shirai Y Kiso S Imai Y Shimomukai H Nomura Y Matsuda Y Matsuzawa Y High levels of transforming growth factor beta 1 in patients with colorectal cancer: association with disease progression Gastroenterology 1996 110 375 382 8566583
  62. [65]Serra R Crowley MR TGF-beta in mammary gland development and breast cancer Breast Dis 2003 18 61 73 15687689
  63. [66]Ronnov-Jessen L Petersen OW Induction of alpha-smooth muscle actin by transforming growth factor-beta 1 in quiescent human breast gland fibroblasts. Implications for myofibroblast generation in breast neoplasia Lab Invest 1993 68 696 707 8515656
  64. [67]Postlethwaite AE Keski-Oja J Moses HL Kang AH Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta J Exp Med 1987 165 251 256 3491869 PMC2188256
  65. [68]Koukourakis MI Giatromanolaki A Harris AL Sivridis E Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma Cancer Res 2006 66 632 637 16423989
  66. [69]Powell DW Mifflin RC Valentich JD Crowe SE Saada JI West AB Myofibroblasts. I. Paracrine cells important in health and disease Am J Physiol 1999 277 C1 C9 10409103
  67. [70]Infante JR Matsubayashi H Sato N Tonascia J Klein AP Riall TA Yeo C Iacobuzio-Donahue C Goggins M Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma J Clin Oncol 2007 25 319 325 17235047
  68. [71]Lukashev ME Werb Z ECM signalling: orchestrating cell behaviour and misbehaviour Trends Cell Biol 1998 8 437 441 9854310
  69. [72]Fukumura D Xavier R Sugiura T Chen Y Park EC Lu N Selig M Nielsen G Taksir T Jain RK Seed B Tumor induction of VEGF promoter activity in stromal cells Cell 1998 94 715 725 9753319
  70. [75]Camps JL Chang SM Hsu TC Freeman MR Hong SJ Zhau HE von Eschenbach AC Chung LW Fibroblast-mediated acceleration of human epithelial tumor growth in vivo Proc Natl Acad Sci U S A 1990 87 75 79 2296606 PMC53202
  71. [76]Imai K Matrix metalloproteinases and cancer cell invasion and metastasis Tanpakushitsu Kakusan Koso 1997 42 1694 1700 9279101
  72. [77]Flavell SJ Hou TZ Lax S Filer AD Salmon M Buckley CD Fibroblasts as novel therapeutic targets in chronic inflammation Br J Pharmacol 2008 153 Suppl 1 S241 S246 17965753 PMC2268075
  73. [78]Thomasset N Lochter A Sympson CJ Lund LR Williams DR Behrendtsen O Werb Z Bissell MJ Expression of autoactivated stromelysin-1 in mammary glands of transgenic mice leads to a reactive stroma during early development Am J Pathol 1998 153 457 467 9708806 PMC1852990
  74. [79]Takahashi M Fukami S Iwata N Inoue K Itohara S Itoh H Haraoka J Saido T In vivo glioma growth requires host-derived matrix metalloproteinase 2 for maintenance of angioarchitecture Pharmacol Res 2002 46 155 163 12220955
  75. [80]Wandel E Grasshoff A Mittag M Haustein UF Saalbach A Fibroblasts surrounding melanoma express elevated levels of matrix metalloproteinase-1 (MMP-1) and intercellular adhesion molecule-1 (ICAM-1) in vitro. Exp Dermatol 2000 9 34 41 10688373
  76. [81]Poola I DeWitty RL Marshalleck JJ Bhatnagar R Abraham J Leffall LD Identification of MMP-1 as a putative breast cancer predictive marker by global gene expression analysis Nat Med 2005 11 481 483 15864312
  77. [82]Sternlicht MD Werb Z How matrix metalloproteinases regulate cell behavior Annu Rev Cell Dev Biol 2001 17 463 516 11687497 PMC2792593
  78. [83]Singer CF Kronsteiner N Marton E Kubista M Cullen KJ Hirtenlehner K Seifert M Kubista E MMP-2 and MMP-9 expression in breast cancer-derived human fibroblasts is differentially regulated by stromal-epithelial interactions Breast Cancer Res Treat 2002 72 69 77 12000221
  79. [84]Wilson CL Heppner KJ Labosky PA Hogan BL Matrisian LM Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin Proc Natl Acad Sci U S A 1997 94 1402 1407 9037065 PMC19803
  80. [85]Balkwill F Mantovani A Inflammation and cancer: back to Virchow? Lancet 2001 357 539 545 11229684
  81. [86]Bucala R Ritchlin C Winchester R Cerami A Constitutive production of inflammatory and mitogenic cytokines by rheumatoid synovial fibroblasts J Exp Med 1991 173 569 574 1997647 PMC2118837
  82. [87]Anderson G Jenkinson EJ Lymphostromal interactions in thymic development and function Nat Rev Immunol 2001 1 31 40 11905812
  83. [88]Parsonage G Falciani F Burman A Filer A Ross E Bofill M Martin S Salmon M Buckley CD Global gene expression profiles in fibroblasts from synovial, skin and lymphoid tissue reveals distinct cytokine and chemokine expression patterns Thromb Haemost 2003 90 688 697 14515190
  84. [89]Buckley CD Pilling D Lord JM Akbar AN Scheel-Toellner D Salmon M Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation Trends Immunol 2001 22 199 204 11274925
  85. [91]Leek RD Harris AL Tumor-associated macrophages in breast cancer J Mammary Gland Biol Neoplasia 2002 7 177 189 12463738
  86. [92]Swann JB Smyth MJ Immune surveillance of tumors J Clin Invest 2007 117 1137 1146 17476343 PMC1857231
  87. [93]Brundula V Rewcastle NB Metz LM Bernard CC Yong VW Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis Brain 2002 125 1297 1308 12023318
  88. [94]Seibert K Masferrer JL Role of inducible cyclooxygenase (COX-2) in inflammation Receptor 1994 4 17 23 8038702
  89. [95]Nakagawa H Liyanarachchi S Davuluri RV Auer H Martin EW Jr de la Chapelle A Frankel WL Role of cancer-associated stromal fibroblasts in metastatic colon cancer to the liver and their expression profiles Oncogene 2004 23 7366 7377 15326482
  90. [96]Baggiolini M Chemokines and leukocyte traffic Nature 1998 392 565 568 9560152
  91. [97]Raingeaud J Pierre J Interleukin-4 downregulates TNFalpha-induced IL-8 production in keratinocytes FEBS Lett 2005 579 3953 3959 16004996
  92. [98]Mueller L Goumas FA Affeldt M Sandtner S Gehling UM Brilloff S Walter J Karnatz N Lamszus K Rogiers X Broering DC Stromal fibroblasts in colorectal liver metastases originate from resident fibroblasts and generate an inflammatory microenvironment Am J Pathol 2007 171 1608 1618 17916596 PMC2043521
  93. [99]Tang DG Patrawala L Calhoun T Bhatia B Choy G Schneider-Broussard R Jeter C Prostate cancer stem/progenitor cells: identification, characterization, and implications Mol Carcinog 2007 46 1 14 16921491
  94. [100]Bonnet D Dick JE Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell Nat Med 1997 3 730 737 9212098
  95. [101]Singh SK Hawkins C Clarke ID Squire JA Bayani J Hide T Henkelman RM Cusimano MD Dirks PB Identification of human brain tumour initiating cells Nature 2004 432 396 401 15549107
  96. [102]Morrison SJ Spradling AC Stem cells and niches: mechanisms that promote stem cell maintenance throughout life Cell 2008 132 598 611 18295578 PMC4505728
  97. [103]Barclay WW Axanova LS Chen W Romero L Maund SL Soker S Lees CJ Cramer SD Characterization of adult prostatic progenitor/stem cells exhibiting self-renewal and multilineage differentiation Stem Cells 2008 26 600 610 18055450 PMC2424224
  98. [104]Sneddon JB Zhen HH Montgomery K van de Rijn M Tward AD West R Gladstone H Chang HY Morganroth GS Oro AE Brown PO Bone morphogenetic protein antagonist gremlin 1 is widely expressed by cancer-associated stromal cells and can promote tumor cell proliferation Proc Natl Acad Sci U S A 2006 103 14842 14847 17003113 PMC1578503
  99. [105]Calabrese C Poppleton H Kocak M Hogg TL Fuller C Hamner B Oh EY Gaber MW Finklestein D Allen M Frank A Bayazitov IT Zakharenko SS Gajjar A Davidoff A Gilbertson RJ A perivascular niche for brain tumor stem cells Cancer Cell 2007 11 69 82 17222791
  100. [106]Sipkins DA Wei X Wu JW Runnels JM Cote D Means TK Luster AD Scadden DT Lin CP In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment Nature 2005 435 969 973 15959517 PMC2570168
  101. [107]De Toni F Racaud-Sultan C Chicanne G Mas VM Cariven C Mesange F Salles JP Demur C Allouche M Payrastre B Manenti S Ysebaert L A crosstalk between the Wnt and the adhesion-dependent signaling pathways governs the chemosensitivity of acute myeloid leukemia Oncogene 2006 25 3113 3122 16407823
  102. [108]Risbridger GP Taylor RA Minireview: regulation of prostatic stem cells by stromal niche in health and disease Endocrinology 2008 149 4303 4306 18535102
  103. [109]Sneddon JB Werb Z Location, location, location: the cancer stem cell niche Cell Stem Cell 2007 1 607 611 18371402 PMC2571117
  104. [110]Sandler RS Halabi S Baron JA Budinger S Paskett E Keresztes R Petrelli N Pipas JM Karp DD Loprinzi CL Steinbach G Schilsky R A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer N Engl J Med 2003 348 883 890 12621132
  105. [111]Loeffler M Kruger JA Niethammer AG Reisfeld RA Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake J Clin Invest 2006 116 1955 1962 16794736 PMC1481657
  106. [113]Reardon DA Akabani G Coleman RE Friedman AH Friedman HS Herndon JE 2nd McLendon RE Pegram CN Provenzale JM Quinn JA Rich JN Vredenburgh JJ Desjardins A Gururangan S Badruddoja M Dowell JM Wong TZ Zhao XG Zalutsky MR Bigner DD Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results J Clin Oncol 2006 24 115 122 16382120
  107. [114]Scott AM Wiseman G Welt S Adjei A Lee FT Hopkins W Divgi CR Hanson LH Mitchell P Gansen DN Larson SM Ingle JN Hoffman EW Tanswell P Ritter G Cohen LS Bette P Arvay L Amelsberg A Vlock D Rettig WJ Old LJ A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer Clin Cancer Res 2003 9 1639 1647 12738716
  108. [115]Yang F Tuxhorn JA Ressler SJ McAlhany SJ Dang TD Rowley DR Stromal expression of connective tissue growth factor promotes angiogenesis and prostate cancer tumorigenesis Cancer Res 2005 65 8887 8895 16204060
  109. [116]Davies B Miles DW Happerfield LC Naylor MS Bobrow LG Rubens RD Balkwill FR Activity of type IV collagenases in benign and malignant breast disease Br J Cancer 1993 67 1126 1131 8494711 PMC1968428
  110. [117]Micke P Ostman A Tumour-stroma interaction: cancer-associated fibroblasts as novel targets in anti-cancer therapy? Lung Cancer 2004 45 Suppl 2 S163 S175 15552797
  111. [118]Fingleton B Matrix metalloproteinase inhibitors for cancer therapy:the current situation and future prospects Expert Opin Ther Targets 2003 7 385 397 12783574
  112. [120]Kong HL Hecht D Song W Kovesdi I Hackett NR Yayon A Crystal RG Regional suppression of tumor growth by in vivo transfer of a cDNA encoding a secreted form of the extracellular domain of the flt-1 vascular endothelial growth factor receptor Hum Gene Ther 1998 9 823 833 9581905
  113. [121]Posey JA Ng TC Yang B Khazaeli MB Carpenter MD Fox F Needle M Waksal H LoBuglio AF A phase I study of anti-kinase insert domain-containing receptor antibody, IMC-1C11, in patients with liver metastases from colorectal carcinoma Clin Cancer Res 2003 9 1323 1332 12684400
  114. [122]Kobayashi H Eckhardt SG Lockridge JA Rothenberg ML Sandler AB O'Bryant CL Cooper W Holden SN Aitchison RD Usman N Wolin M Basche ML Safety and pharmacokinetic study of RPI.4610 (ANGIOZYME), an anti-VEGFR-1 ribozyme, in combination with carboplatin and paclitaxel in patients with advanced solid tumors Cancer Chemother Pharmacol 2005 56 329 336 15906031
  115. [123]Zukiel R Nowak S Wyszko E Rolle K Gawronska I Barciszewska MZ Barciszewski J Suppression of human brain tumor with interference RNA specific for tenascin-C Cancer Biol Ther 2006 5 1002 1007 16775434
  116. [124]Adams S Miller GT Jesson MI Watanabe T Jones B Wallner BP PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism Cancer Res 2004 64 5471 5480 15289357
  117. [125]Wuest T Moosmayer D Pfizenmaier K Construction of a bispecific single chain antibody for recruitment of cytotoxic T cells to the tumour stroma associated antigen fibroblast activation protein J Biotechnol 2001 92 159 168 11640985
  118. [126]Samel D Muller D Gerspach J Assohou-Luty C Sass G Tiegs G Pfizenmaier K Wajant H Generation of a FasL-based proapoptotic fusion protein devoid of systemic toxicity due to cell-surface antigen-restricted Activation J Biol Chem 2003 278 32077 32082 12773535
  119. [127]Leighl NB Paz-Ares L Douillard JY Peschel C Arnold A Depierre A Santoro A Betticher DC Gatzemeier U Jassem J Crawford J Tu D Bezjak A Humphrey JS Voi M Galbraith S Hann K Seymour L Shepherd FA Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18 J Clin Oncol 2005 23 2831 2839 15837997
  120. [128]Aikawa T Gunn J Spong SM Klaus SJ Korc M Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer Mol Cancer Ther 2006 5 1108 1116 16731742
  121. [129]Kondo S Tanaka N Kubota S Mukudai Y Yosimichi G Sugahara T Takigawa M Novel angiogenic inhibitor DN-9693 that inhibits post-transcriptional induction of connective tissue growth factor (CTGF/CCN2) by vascular endothelial growth factor in human endothelial cells Mol Cancer Ther 2006 5 129 137 16432171
  122. [130]Bramhall SR Hallissey MT Whiting J Scholefield J Tierney G Stuart RC Hawkins RE McCulloch P Maughan T Brown PD Baillet M Fielding JW Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial Br J Cancer 2002 86 1864 1870 12085177 PMC2375430
  123. [131]Hirte H Vergote IB Jeffrey JR Grimshaw RN Coppieters S Schwartz B Tu D Sadura A Brundage M Seymour L A phase III randomized trial of BAY 12–9566 (tanomastat) as maintenance therapy in patients with advanced ovarian cancer responsive to primary surgery and paclitaxel/platinum containing chemotherapy: a National Cancer Institute of Canada Clinical Trials Group Study Gynecol Oncol 2006 102 300 308 16442153
  124. [132]Qu CF Song EY Li Y Rizvi SM Raja C Smith R Morgenstern A Apostolidis C Allen BJ Pre-clinical study of 213Bi labeled PAI2 for the control of micrometastatic pancreatic cancer Clin Exp Metastasis 2005 22 575 586 16475028
  125. [133]Kobayashi H Sugino D She MY Ohi H Hirashima Y Shinohara H Fujie M Shibata K Terao T A bifunctional hybrid molecule of the amino-terminal fragment of urokinase and domain II of bikunin efficiently inhibits tumor cell invasion and metastasis Eur J Biochem 1998 253 817 826 9654084
  126. [134]Bleumer I Knuth A Oosterwijk E Hofmann R Varga Z Lamers C Kruit W Melchior S Mala C Ullrich S De Mulder P Mulders PF Beck J A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients Br J Cancer 2004 90 985 990 14997194 PMC2410216

Cited by

Sorted by citations

Authors
Xing, F.
Affiliations
SIU Medicine (US)
Corresponding author
Xing, Fei
ORCID
Xing, Fei
Venue
Frontiers in Bioscience
Publisher
IMR Press
Published
2010
Volume
15
Issue
1
Pages
166
ISSN
  • 1093-4715 (ISSN-L)
  • 1093-9946
DOI
10.2741/3613
PMC
PMC2905156
OpenAlex
W2075261412
Cited by
682
References
8
Citations by year
2026: 25 · 2025: 40 · 2024: 54 · 2023: 59 · 2022: 49 · 2021: 61 · 2020: 67 · 2019: 49 · 2018: 63 · 2017: 38 · 2016: 38 · 2015: 33 · 2014: 29 · 2013: 39 · 2012: 21
FWCI
6.33
Type
journal article
Language
en
Open access
Locations
  • Frontiers in bioscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (R01CA129000, R01CA124650)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Keywords
cancer-associated fibroblasts, tumor microenvironment, CAF heterogeneity, CAF origin, tumor progression, metastasis, carcinogenesis, CAF-targeted therapy
MeSH terms
Animals, Cell Transformation, Neoplastic, Epithelial Cells, Fibroblasts, Humans, Mesoderm, Models, Biological, Neoplasms, Biomarkers, Tumor, Endothelial Cells

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