Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development
Open accessAbstract
Hypoxia, or low oxygen tension, is a major regulator of tumor development and aggressiveness. However, how cancer cells adapt to hypoxia and communicate with their surrounding microenvironment during tumor development remain important questions. Here, we show that secreted vesicles with exosome characteristics mediate hypoxia-dependent intercellular signaling of the highly malignant brain tumor glioblastoma multiforme (GBM). In vitro hypoxia experiments with glioma cells and studies with patient materials reveal the enrichment in exosomes of hypoxia-regulated mRNAs and proteins (e.g., matrix metalloproteinases, IL-8, PDGFs, caveolin 1, and lysyl oxidase), several of which were associated with poor glioma patient prognosis. We show that exosomes derived from GBM cells grown at hypoxic compared with normoxic conditions are potent inducers of angiogenesis ex vivo and in vitro through phenotypic modulation of endothelial cells. Interestingly, endothelial cells were programmed by GBM cell-derived hypoxic exosomes to secrete several potent growth factors and cytokines and to stimulate pericyte PI3K/AKT signaling activation and migration. Moreover, exosomes derived from hypoxic compared with normoxic conditions showed increased autocrine, promigratory activation of GBM cells. These findings were correlated with significantly enhanced induction by hypoxic compared with normoxic exosomes of tumor vascularization, pericyte vessel coverage, GBM cell proliferation, as well as decreased tumor hypoxia in a mouse xenograft model. We conclude that the proteome and mRNA profiles of exosome vesicles closely reflect the oxygenation status of donor glioma cells and patient tumors, and that the exosomal pathway constitutes a potentially targetable driver of hypoxia-dependent intercellular signaling during tumor development.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Exosomes are a subclass of extracellular vesicles with a size of 30-100 nm and act as important mediators of signaling between tumor cells and other cells in the microenvironment.
“Exosomes are a subclass of EVs with a size of 30–100 nm, with a recognized role as an important mediator of signaling event between tumor cells and other cells in its microenvironment (8, 9).”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [9]
GBM cells employ exosomes for tumor cell/microenvironment communications and to facilitate proliferation, invasion, and metastatic behaviors.
“Similar to other cancer cell types, GBM cells employ exosomes for tumor cells/microenvironment communications and to facilitate its proliferation, invasion, and metastatic behaviors (8, 9).”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [9]
Diverse types of cells including neurons can secrete exosomes, which transfer functional proteins, mRNAs and/or microRNAs to recipient cells.
“Diverse types of cells including neurons can secrete exosomes, which transfer functional proteins11,12, mRNAs and/or microRNAs (miRNAs)13,14 to recipient cells.”
From Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity (2017) · cites this paper as [12]
Exosomes isolated from plasma of GBM patients contain increased amounts of hypoxia-regulated proteins including MMP9, MMP8, PDGF, PAI1, and IGFBP3 compared to exosomes from sex- and age-matched controls.
“Interestingly, exosomes isolated from the plasma of GBM patients contain increased amounts of hypoxia-regulated proteins— including MMP9, MMP8, platelet-derived growth factor (PDGF), PAI1, and insulin-like growth factor–binding protein 3 (IGFBP3)—compared to exosomes isolated from plasma of sex- and age-matched controls (105).”
From Hypoxic control of metastasis (2016) · cites this paper as [105]
Exosomes mediate hypoxia-dependent stimulation of angiogenesis in glioblastoma multiforme through activation of paracrine signaling in endothelial cells and pericytes.
“Recent studies have shown that exosomes mediate hypoxia-dependent stimulation of angiogenesis in glioblastoma multiforme (GBM) through the activation of paracrine signaling in endothelial cells and pericytes (105).”
From Hypoxic control of metastasis (2016) · cites this paper as [105]
Hypoxia stimulates the release of extracellular vesicles that promote angiogenesis.
“Hypoxia stimulates the release of extracellular vesicles that promote angiogenesis [93–97] and increased exosome formation by hypoxic cancer cells requires HIF activity [96, 98], but the relevant HIF target genes have not been identified.”
From The hypoxic tumor microenvironment: A driving force for breast cancer progression (2016) · cites this paper as [96]
Increased exosome formation by hypoxic cancer cells requires HIF activity.
“Hypoxia stimulates the release of extracellular vesicles that promote angiogenesis [93–97] and increased exosome formation by hypoxic cancer cells requires HIF activity [96, 98], but the relevant HIF target genes have not been identified.”
From The hypoxic tumor microenvironment: A driving force for breast cancer progression (2016) · cites this paper as [96]
Hypoxia-induced extracellular vesicle formation is a means by which cancer cells influence the phenotype of vascular and other stromal cells.
“Previous studies implicated hypoxia-induced extracellular vesicle formation as a means by which cancer cells influence the phenotype of vascular and other stromal cells [93–96], whereas HIF- and RAB22A-dependent microvesicle formation increases the invasive and metastatic properties of a primary breast tumor by transferring the phenotype of hypoxic BCCs to non-hypoxic BCCs [100].”
From The hypoxic tumor microenvironment: A driving force for breast cancer progression (2016) · cites this paper as [96]
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007) · Nature Cell Biology · doi:10.1038/ncb1596 · Cited by 12,834 · see citing works
Hypoxia — a key regulatory factor in tumour growth
Harris, A. L. (2002) · Nature Reviews Cancer · doi:10.1038/nrc704 · Cited by 5,177 · see citing works
Skog, J., Würdinger, T., van Rijn, S., Meijer, D. H., Gainche, L., Curry, W. T., Carter, B. S., Krichevsky, A. M., & Breakefield, X. O. (2008) · Nature Cell Biology · doi:10.1038/ncb1800 · Cited by 5,001 · see citing works
Membrane vesicles as conveyors of immune responses
Théry, C., Ostrowski, M., & Segura, É. (2009) · Nature reviews. Immunology · doi:10.1038/nri2567 · Cited by 3,869 · see citing works
Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET
Peinado, H., Alečković, M., Lavotshkin, S., Matei, I., Costa-Silva, B., Moreno-Bueno, G., Hergueta-Redondo, M., Williams, C., García-Santos, G., Ghajar, C. M., et al. (2012) · Nature Medicine · doi:10.1038/nm.2753 · Cited by 3,715 · see citing works
B lymphocytes secrete antigen-presenting vesicles.
Raposo, G., Nijman, H. W., Stoorvogel, W., Liejendekker, R., Harding, C. V., Melief, C. J., & Geuze, H. J. (1996) · The Journal of experimental medicine · doi:10.1084/jem.183.3.1161 · Cited by 3,546 · see citing works
Targeting hypoxia in cancer therapy
Wilson, W. R., & Hay, M. P. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3064 · Cited by 3,172 · see citing works
Rab27a and Rab27b control different steps of the exosome secretion pathway
Ostrowski, M., Carmo, N., Krumeich, S., Fanget, I., Raposo, G., Savina, A., Moita, C. F., Schauer, K., Hume, A. N., Freitas, R. P., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb2000 · Cited by 2,761 · see citing works
Pericytes: Developmental, Physiological, and Pathological Perspectives, Problems, and Promises
Armulik, A., Genové, G., & Betsholtz, C. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.07.001 · Cited by 2,653 · see citing works
Angiogenesis as a therapeutic target
Ferrara, N., & Kerbel, R. S. (2005) · Nature · doi:10.1038/nature04483 · Cited by 2,653 · see citing works
Regulation of angiogenesis by hypoxia: role of the HIF system
Pugh, C. W., & Ratcliffe, P. J. (2003) · Nature Medicine · doi:10.1038/nm0603-677 · Cited by 2,520 · see citing works
Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells
Al-Nedawi, K. N. I., Meehan, B., Micallef, J., Lhotak, V., May, L. L., Guha, A., & Rak, J. W. (2008) · Nature Cell Biology · doi:10.1038/ncb1725 · Cited by 2,037 · see citing works
Shedding microvesicles: artefacts no more
Cocucci, E., Racchetti, G., & Meldolesi, J. (2009) · Trends in Cell Biology · doi:10.1016/j.tcb.2008.11.003 · Cited by 1,742 · see citing works
Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics
Semenza, G. L. (2010) · Oncogene · doi:10.1038/onc.2009.441 · Cited by 1,712 · see citing works
Hypoxia signalling in cancer and approaches to enforce tumour regression
Pouysségur, J., Dayan, F., & Mazure, N. M. (2006) · Nature · doi:10.1038/nature04871 · Cited by 1,676 · see citing works
The impact of O2 availability on human cancer
Bertout, J. A., Patel, S. A., & Simon, M. C. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2540 · Cited by 1,365 · see citing works
Ratajczak, J., Wysoczynski, M., Hayek, F., Janowska-Wieczorek, A., & Ratajczak, M. Z. (2006) · Leukemia · doi:10.1038/sj.leu.2404296 · Cited by 1,340 · see citing works
Hypoxic enhancement of exosome release by breast cancer cells
King, H. W., Michael, M. Z., & Gleadle, J. M. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-421 · Cited by 1,045 · see citing works
High Levels of Exosomes Expressing CD63 and Caveolin-1 in Plasma of Melanoma Patients
Logozzi, M., Milito, A. D., Lugini, L., Borghi, M., Calabrò, L., Spada, M., Perdicchio, M., Marino, M. L., Federici, C., Iessi, E., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005219 · Cited by 959 · see citing works
The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis
Brat, D. J., Bellail, A. C., & Meir, E. G. V. (2005) · Neuro-Oncology · doi:10.1215/s1152851704001061 · Cited by 760 · see citing works
Hypoxia: A key regulator of angiogenesis in cancer
Liao, D., & Johnson, R. S. (2007) · Cancer and Metastasis Reviews · doi:10.1007/s10555-007-9066-y · Cited by 720 · see citing works
The brain tumor microenvironment
Charles, N. A., Holland, E. C., Gilbertson, R., Glass, R., & Kettenmann, H. (2011) · Glia · doi:10.1002/glia.21136 · Cited by 718 · see citing works
The brain tumor microenvironment
Charles, N. A., Holland, E. C., Gilbertson, R. J., Glaß, R., & Kettenmann, H. (2011) · Glia · doi:10.1002/glia.21264 · Cited by 712 · see citing works
Al-Nedawi, K. N. I., Meehan, B., Kerbel, R. S., ALLISON, A. C., & Rak, J. W. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804543106 · Cited by 666 · see citing works
Bobrie, A., Krumeich, S., Reyal, F., Recchi, C., Moita, L. F., Seabra, M. C., Ostrowski, M., & Théry, C. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0925 · Cited by 647 · see citing works
Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis
Kaur, B., Khwaja, F. W., Severson, E. A., Matheny, S. L., Brat, D. J., & Van Meir, E. G. (2005) · Neuro-Oncology · doi:10.1215/s1152851704001115 · Cited by 599 · see citing works
Park, J. E., Tan, H. S., Datta, A., Lai, R. C., Zhang, H., Meng, W., Lim, S. K., & Sze, S. K. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m900381-mcp200 · Cited by 582 · see citing works
Antonyak, M. A., Li, B., Boroughs, L. K., Johnson, J. L., Druso, J. E., Bryant, K. L., Holowka, D. A., & Cerione, R. A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017667108 · Cited by 497 · see citing works
Microvesicles: Messengers and mediators of tumor progression
Al-Nedawi, K. N. I., Meehan, B., & Rak, J. W. (2009) · Cell Cycle · doi:10.4161/cc.8.13.8988 · Cited by 401 · see citing works
Hypoxia, inflammation, and the tumor microenvironment in metastatic disease
Finger, E. C., & Giaccia, A. J. (2010) · Cancer and Metastasis Reviews · doi:10.1007/s10555-010-9224-5 · Cited by 370 · see citing works
Hypoxia Is Important in the Biology and Aggression of Human Glial Brain Tumors
Evans, S. M., Judy, K. D., Dunphy, I., Jenkins, W. T., Hwang, W., Nelson, P. T., Lustig, R. A., Jenkins, K. W., Magarelli, D. P., Hahn, S. M., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-1081 · Cited by 356 · see citing works
Sallinen, S. L., Sallinen, P. K., Haapasalo, H. K., et al. (2000) · PubMed · Cited by 330 · see citing works
Franco, M., Roswall, P., Cortez, E., Hanahan, D., & Pietras, K. (2011) · Blood · doi:10.1182/blood-2011-01-331694 · Cited by 310 · see citing works
U87MG Decoded: The Genomic Sequence of a Cytogenetically Aberrant Human Cancer Cell Line
Clark, M. J., Homer, N., O’Connor, B. D., Chen, Z., Eskin, A., Lee, H., Merriman, B., & Nelson, S. F. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000832 · Cited by 306 · see citing works
Antiangiogenic therapy, hypoxia, and metastasis: risky liaisons, or not?
De Bock, K., Mazzone, M., & Carmeliet, P. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.83 · Cited by 293 · see citing works
Svensson, K. J., Kucharzewska, P., Christianson, H. C., Sköld, S., Löfstedt, T., Johansson, M. C., Mörgelin, M., Bengzon, J., Ruf, W., & Belting, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104261108 · Cited by 288 · see citing works
Self-citationToustrup, K., Sørensen, B. S., Nordsmark, M., Busk, M., Wiuf, C., Alsner, J., & Overgaard, J. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1182 · Cited by 259 · see citing works
Genome-wide association study of glioma and meta-analysis
Rajaraman, P., Melin, B. S., Wang, Z., McKean‐Cowdin, R., Michaud, D. S., WANG, S. S., Bondy, M. L., Houlston, R. S., Jenkins, R. B., Wrensch, M., et al. (2012) · Human Genetics · doi:10.1007/s00439-012-1212-0 · Cited by 239 · see citing works
Migration of capillary endothelial cells is stimulated by tumour-derived factors
Zetter, B. R. (1980) · Nature · doi:10.1038/285041a0 · Cited by 226 · see citing works
Belting, M., & Wittrup, A. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200810038 · Cited by 163 · see citing works
Self-citationAbulrob, A., Giuseppin, S., Andrade, M. F., McDermid, A., Moreno, M., & Stanimirovic, D. B. (2004) · Oncogene · doi:10.1038/sj.onc.1207911 · Cited by 147 · see citing works
Wang, Y., Roche, O., Xu, C., Moriyama, E. H., Heir, P., Chung, J., Roos, F. C., Chen, Y., Finak, G., Milosevic, M., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112129109 · Cited by 137 · see citing works
The Unconventional Secretory Machinery of Fibroblast Growth Factor 2
Nickel, W. (2011) · Traffic · doi:10.1111/j.1600-0854.2011.01187.x · Cited by 76 · see citing works
Caveolin-1, caveolae, and glioblastoma
Parat, M., & Riggins, G. J. (2012) · Neuro-Oncology · doi:10.1093/neuonc/nos079 · Cited by 70 · see citing works
Marotta, D. E., Karar, J., Jenkins, W. T., Kumanova, M., Jenkins, K. W., Tobias, J. W., Baldwin, D. A., Hatzigeorgiou, A. G., Alexiou, P., Evans, S. M., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3061 · Cited by 55 · see citing works
Cassoni, P., Senetta, R., Castellano, I., et al. (2007) · The American Journal of Surgical Pathology · doi:10.1097/01.pas.0000213433.14740.5d · Cited by 36 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The biology <b>,</b> function <b>,</b> and biomedical applications of exosomes
Kalluri, R., & LeBleu, V. S. (2020) · Science · doi:10.1126/science.aau6977 · Cited by 10,770 · see citing works
Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles
Colombo, M., Raposo, G., & Théry, C. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101512-122326 · Cited by 6,186 · see citing works
Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis
Becker, A., Thakur, B. K., Weiss, J. M., Kim, H. S., Peinado, H., & Lyden, D. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.10.009 · Cited by 2,003 · see citing works
Ha, D., Yang, N., & Nadithe, V. (2016) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2016.02.001 · Cited by 1,346 · see citing works
Rankin, E. B., & Giaccia, A. J. (2016) · Science · doi:10.1126/science.aaf4405 · Cited by 1,340 · see citing works
Zhang, Y., Bi, J., Huang, J., Tang, Y., Du, S., & Li, P. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s264498 · Cited by 1,323 · see citing works
Christianson, H. C., Svensson, K. J., van Kuppevelt, T. H., Li, J.-P., & Belting, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1304266110 · Cited by 903 · see citing works
Self-citationJohnsen, K. B., Gudbergsson, J. M., Skov, M. N., Pilgaard, L., Moos, T., & Duroux, M. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.04.005 · Cited by 704 · see citing works
The hypoxic tumor microenvironment: A driving force for breast cancer progression
Semenza, G. L. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.05.036 · Cited by 535 · see citing works
Wang, T., Gilkes, D. M., Takano, N., Xiang, L., Luo, W., Bishop, C. J., Chaturvedi, P., Green, J. J., & Semenza, G. L. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410041111 · Cited by 493 · see citing works
Mechanisms associated with biogenesis of exosomes in cancer
McAndrews, K. M., & Kalluri, R. (2019) · Molecular Cancer · doi:10.1186/s12943-019-0963-9 · Cited by 394 · see citing works
Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity
Xu, B., Zhang, Y., Du, X.-F., Li, J., Zi, H.-X., Bu, J.-W., Yan, Y., Han, H., & Du, J.-L. (2017) · Cell Research · doi:10.1038/cr.2017.62 · Cited by 354 · see citing works
Monfared, H., Jahangard, Y., Nikkhah, M., Mirnajafi-Zadeh, J., & Mowla, S. J. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00782 · Cited by 123 · see citing works
“subclass of EVs with a size of 30–100 nm, with a recognized role as an important mediator of signaling event between tumor cells and other cells in its microenvironment (8, 9).”
BackgroundExtracellular Vesicles in Brain Tumors and Neurodegenerative Diseases
Ciregia, F., Urbani, A., & Palmisano, G. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00276 · Cited by 110 · see citing works
Sullivan, R., Maresh, G., Zhang, X., Salomon, C., Hooper, J., Margolin, D., & Li, L. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00194 · Cited by 112 · see citing works
Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy
Wang, X., Wang, L., Lin, H., Zhu, Y., Huang, D., Lai, M., Xi, X., Huang, J., Zhang, W., & Zhong, T. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1303335 · Cited by 112 · see citing works
Exosomes as Emerging Pro-Tumorigenic Mediators of the Senescence-Associated Secretory Phenotype
Jakhar, R., & Crasta, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20102547 · Cited by 98 · see citing works
Exosomes in neurologic and psychiatric disorders
Tsilioni, I., Panagiotidou, S., & Theoharides, T. C. (2014) · Clinical Therapeutics · doi:10.1016/j.clinthera.2014.05.005 · Cited by 93 · see citing works
Microglia communication: parallels between aging and Alzheimer's disease
Udeochu, J. C., Shea, J. M., & Villeda, S. A. (2016) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12307 · Cited by 87 · see citing works
- Authors
- Kucharzewska, P., Christianson, H. C., Welch, J. E., Svensson, K. J., Fredlund, E., Ringnér, M., Mörgelin, M., Bourseau-Guilmain, E., Bengzon, J., & Belting, M.
- Affiliations
- Lund University (SE)
- Karolinska Institutet (SE)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-04-15
- Volume
- 110
- Issue
- 18
- Pages
- 7312-7317
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3645587
- OpenAlex
- W2081124475
- Cited by
- 939
- References
- 47
- Citations by year
- 2026: 28 · 2025: 39 · 2024: 67 · 2023: 56 · 2022: 101 · 2021: 110 · 2020: 93 · 2019: 89 · 2018: 85 · 2017: 73 · 2016: 54 · 2015: 60 · 2014: 68 · 2013: 16
- FWCI
- 29.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- exosomes, glioblastoma, tumor hypoxia, intercellular communication, angiogenesis, endothelial cells, pericytes, PI3K/Akt signaling, tumor microenvironment, exosomal cargo, matrix metalloproteinases, interleukin-8, platelet-derived growth factor, caveolin-1, lysyl oxidase, tumor vascularization, cell migration, autocrine activation, cancer prognosis
- MeSH terms
- Animals, Blood Vessels, Brain Neoplasms, Cell Transformation, Neoplastic, Female, Glioma, Humans, Neoplasm Proteins, Neovascularization, Pathologic, Tissue Donors, Signal Transduction, Cell Hypoxia, Gene Expression Regulation, Neoplastic, Mice, SCID, Autocrine Communication, Paracrine Communication, Pericytes, Proteome, Xenograft Model Antitumor Assays, Endothelial Cells, Cell Line, Tumor, Mice, Exosomes, Transcriptome
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
