Abstract
Recently, it has become clearer that tumor plasticity increases the chance that cancer cells could acquire new mechanisms to escape immune surveillance, become resistant to conventional drugs, and spread to distant sites.
Effectively, tumor plasticity drives adaptive response of cancer cells to hypoxia and nutrient deprivation leading to stimulation of neoangionesis or tumor escape. Therefore, tumor plasticity is believed to be a great contributor in recurrence and metastatic dissemination of cancer cells. Importantly, it could be an Achilles’ heel of cancer if we could identify molecular mechanisms dictating this phenotype.
The reactivation of stem-like signalling pathways is considered a great determinant of tumor plasticity; in addition, a key role has been also attributed to tumor microenvironment (TME). Indeed, it has been proved that cancer cells interact with different cells in the surrounding extracellular matrix (ECM). Interestingly, well-established communication represents a potential allied in maintenance of a plastic phenotype in cancer cells supporting tumor growth and spread. An important signalling pathway mediating cancer cell-TME crosstalk is represented by the HGF/c-Met signalling.
Here, we review the role of the HGF/c-Met signalling in tumor-stroma crosstalk focusing on novel findings underlying its role in tumor plasticity, immune escape, and development of adaptive mechanisms.
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References
Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752
van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415(6871):530–536
De Sousa EMF, Wang X, Jansen M, Fessler E, Trinh A, de Rooij LP, de Jong JH, de Boer OJ, van Leersum R, Bijlsma MF et al (2013) Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat Med 19:614–618
Marisa L, de Reynies A, Duval A, Selves J, Gaub MP, Vescovo L, Etienne-Grimaldi MC, Schiappa R, Guenot D, Ayadi M et al (2013) Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 10:e1001453
Sadanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S, Ostos LC, Lannon WA, Grotzinger C, Del Rio M et al (2013) A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 19:619–625
Magee JA, Piskounova E, Morrison SJ (2012) Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 21(3):283–296
Prasetyanti PR, Medema JP (2017) Intra-tumor heterogeneity from a cancer stem cell perspective. Mol Cancer 16(1):41
Plaks V, Kong N, Werb Z (2015) The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell 16(3):225–238
Kreso A, Dick JE (2014) Evolution of the cancer stem cell model. Cell Stem Cell 14(3):275–291
Dalerba P, Cho RW, Clarke MF (2007) Cancer stem cells: models and concepts. Annu Rev Med 58:267–284
Diehn M, Cho RW, Clarke MF (2009) Therapeutic implications of the cancer stem cell hypothesis. Semin Radiat Oncol 19(2):78–86
Boccaccio C, Comoglio PM (2006) Invasive growth: a MET-driven genetic programme for cancer stem cells. Nat Rev Cancer. 6(8):637–645
Stoker M, Gherardi E, Perryman M, Gray J (1987) Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature. 327(6119):239–242
Naldini L, Weidner KM, Vigna E, Gaudino G, Bardelli A, Ponzetto C, Narsimhan RP, Hartmann G, Zarnegar R, Michalopoulos GK et al (1991) Scatter factor and hepatocyte growth factor are indistinguishable ligands for the met receptor. EMBO J. 10(10):2867–2878
Weidner KM, Di Cesare S, Sachs M et al (1996) Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis. Nature 384:173–176
Graziani A, Gramaglia D, dalla Zonca P et al (1993) Hepatocyte growth factor/scatter factor stimulates the Ras-guanine nucleotide exchanger. J Biol Chem 268:9165–9168
Xiao GH, Jeffers M, Bellacosa A et al (2001) Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Proc Natl Acad Sci U S A 98:247–252
Syed ZA, Yin W, Hughes K et al (2011) HGF/c-met/Stat3 signaling during skin tumor cell invasion: indications for a positive feedback loop. BMC Cancer 11:180
Sangwan V, Paliouras GN, Cheng A et al (2006) Protein tyrosine phosphatase 1B deficiency protects against Fas induced hepatic failure. J Biol Chem 281:221–228
Organ SL, Tsao MS (2011) An overview of the c-MET signaling pathway. Ther Adv Med Oncol 3:S7–S19
Trusolino L, Bertotti A, Comoglio PM (2010) MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol 11:834–848
Tsarfaty I, Rong S, Resau JH, Rulong S, da Silva PP, Vande Woude GF (1994) The Met proto-oncogene mesenchymal to epithelial cell conversion. Science 263(5143):98–101
Andermarcher E, Surani MA, Gherardi E (1996) Co-expression of the HGF/SF and c-met genes during early mouse embryogenesis precedes reciprocal expression in adjacent tissues during organogenesis. Dev Genet 18(3):254–266
Sonnenberg E, Meyer D, Weidner KM, Birchmeier C (1993) Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development. J Cell Biol. 123(1):223–235
Latimer AJ, Jessen JR (2008) Hgf/c-met expression and functional analysis during zebrafish embryogenesis. Dev Dyn. 237(12):3904–3915
Huh CG, Factor VM, Sánchez A, Uchida K, Conner EA, Thorgeirsson SS (2004) Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci U S A. 101(13):4477–4482
Borowiak M, Garratt AN, Wüstefeld T, Strehle M, Trautwein C, Birchmeier C (2004) Met provides essential signals for liver regeneration. Proc Natl Acad Sci U S A. 101(29):10608–10613
Ma H, Saenko M, Opuko A, Togawa A, Soda K, Marlier A, Moeckel GW, Cantley LG, Ishibe S (2009) Deletion of the Met receptor in the collecting duct decreases renal repair following ureteral obstruction. Kidney Int 76:868–876
Perdomo G, Martinez-Brocca MA, Bhatt BA, Brown NF, O’Doherty RM, Garcia-Ocaña A (2008) Hepatocyte growth factor is a novel stimulator of glucose uptake and metabolism in skeletal muscle cells. J Biol Chem. 283(20):13700–13706
Fafalios A, Ma J, Tan X, Stoops J, Luo J, Defrances MC, Zarnegar R (2011) A hepatocyte growth factor receptor (Met)-insulin receptor hybrid governs hepatic glucose metabolism. Nat Med. 17(12):1577–1584
GarcĂa-Ocaña A, Vasavada RC, Cebrian A, Reddy V, Takane KK, LĂłpez-Talavera JC, Stewart AF (2001) Transgenic overexpression of hepatocyte growth factor in the beta-cell markedly improves islet function and islet transplant outcomes in mice. Diabetes. 50(12):2752–2762
Oliveira AG, AraĂşjo TG, Carvalho BM, Rocha GZ, Santos A, Saad MJA (2018) The Role of Hepatocyte Growth Factor (HGF) in insulin resistance and diabetes. Front Endocrinol (Lausanne) 9:503
Dai C, Huh CG, Thorgeirsson SS, Liu Y (2005) Beta-cell-specific ablation of the hepatocyte growth factor receptor results in reduced islet size, impaired insulin secretion, and glucose intolerance. Am J Pathol. 167:429–436. https://doi.org/10.1016/S0002-9440(10)62987-2
Ilangumaran S, Villalobos-Hernandez A, Bobbala D, Ramanathan S (2016) The hepatocyte growth factor (HGF)-MET receptor tyrosine kinase signaling pathway: diverse roles in modulating immune cell functions. Cytokine. 82:125–139
Ding S, Merkulova-Rainon T, Han ZC, Tobelem G (2003) HGF receptor up-regulation contributes to the angiogenic phenotype of human endothelial cells and promotes angiogenesis in vitro. Blood. 101(12):4816–4822
Thompson BL, Levitt P (2015) Complete or partial reduction of the Met receptor tyrosine kinase in distinct circuits differentially impacts mouse behavior. J Neurodev Disord 7:35
Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G (2012) Targeting MET in cancer: rationale and progress. Nat Rev Cancer. 12(2):89–103
Danilkovitch-Miagkova A, Zbar B (2002) Dysregulation of Met receptor tyrosine kinase activity in invasive tumors. J Clin Invest 109:863–867
Beroukhim R, Getz G, Nghiemphu L, Barretina J, Hsueh T, Linhart D et al (2007) Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc Natl Acad Sci U S A 104:20007–20012
Tong CY, Hui AB, Yin XL, Pang JC, Zhu XL, Poon WS et al (2004) Detection of oncogene amplifications in medulloblastomas by comparative genomic hybridization and array-based comparative genomic hybridization. J Neurosurg 100:187–193
Cappuzzo F, Marchetti A, Skokan M, Rossi E, Gajapathy S, Felicioni L, Del Grammastro M, Sciarrotta MG, Buttitta F, Incarbone M, Toschi L, Finocchiaro G, Destro A, Terracciano L, Roncalli M, Alloisio M, Santoro A, Varella-Garcia M (2009) Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. J Clin Oncol. 27(10):1667–1674
Umeki K, Shiota G, Kawasaki H (1999) Clinical significance of c-met oncogene alterations in human colorectal cancer. Oncology 56:314–312
Schmidt LS, Nickerson ML, Angeloni D, Glenn GM, Walther MM, Albert PS, Warren MB, Choyke PL, Torres-Cabala CA, Merino MJ, Brunet J, Berez V, Borras J, Sesia G, Middelton L, Phillips JL, Stolle C, Zbar B, Pautler SE, Linehan WM (2004) Early onset hereditary papillary renal carcinoma: germline missense mutations in the tyrosine kinase domain of the met proto-oncogene. J Urol. 172(4 Pt 1):1256–1261
Tanyi J, Tory K, Rigó J Jr, Nagy B, Papp Z (1999) Evaluation of the tyrosine kinase domain of the Met protooncogene in sporadic ovarian carcinomas. Pathol Oncol Res. 5(3):187–191
Lee JH, Han SU, Cho H, Jennings B, Gerrard B, Dean M, Schmidt L, Zbar B, Vande Woude GF (2000) A novel germ line juxta-membrane Met mutation in human gastric cancer. Oncogene 19:4947–4953
Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, Griffin JD, Johnson BE, Salgia R (2003) c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 63:6272–6281
Wasenius VM, Hemmer S, Karjalainen-Lindsberg ML, Nupponen NN, Franssila K, Joensuu H (2005) MET receptor tyrosine kinase sequence alterations in differentiated thyroid carcinoma. Am J Surg Pathol 29(4):544–549
Park WS, Dong SM, Kim SY, Na EY, Shin MS, Pi JH, Kim BJ, Bae JH, Hong YK, Lee KS, Lee SH, Yoo NJ, Jang JJ, Pack S, Zhuang Z, Schmidt L, Zbar B, Lee JY (1999) Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res. 59(2):307–310
Kataoka H, Hamasuna R, Itoh H, Kitamura N, Koono M (2000) Activation of hepatocyte growth factor/scatter factor in colorectal carcinoma. Cancer Res. 60:6148–6159
Parr C, Watkins G, Mansel RE, Jiang WG (2004) The hepatocyte growth factor regulatory factors in human breast cancer. Clin. Cancer Res. 10:202–211
Szabo R, Rasmussen AL, Moyer AB, Kosa P, Schafer JM, Molinolo AA, Gutkind JS, Bugge TH (2011) c-MET-induced epithelial carcinogenesis is initiated by the serine protease matriptase. Oncogene 30:2003–2016
Fukuura T, Miki C, Inoue T, Matsumoto K, Suzuki H (1998) Serum hepatocyte growth factor as an index of disease status of patients with colorectal carcinoma. Br J Cancer. 78(4):454–459
Toiyama Y, Miki C, Inoue Y, Okugawa Y, Tanaka K, Kusunoki M (2009) Serum hepatocyte growth factor as a prognostic marker for stage II or III colorectal cancer patients. Int J Cancer. 125(7):1657–1662
Taniguchi T, Toi M, Inada K, Imazawa T, Yamamoto Y, Tominaga T (1995) Serum concentrations of hepatocyte growth factor in breast cancer patients. Clin Cancer Res. 1(9):1031–1034
Qian C-N, Guo X, Cao B, Kort EJ, Lee C-C, Chen J, Wang L-M, Mai W-Y, Min H-Q, Hong M-H, Vande GF, Woude JH (2002) Resau and Bin Tean Met protein expression level correlates with survival in patients with late-stage Nasopharyngeal Carcinoma. Cancer Res. 62(2):589–596
Lesko E, Majka M (2008) The biological role of HGF-MET axis in tumor growth and development of metastasis. Front Biosci. 13:1271–1280
Zeng ZS, Weiser MR, Kuntz E (2008) c-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases. Cancer Lett 265:258–269
Orian-Rousseau V, Chen L, Sleeman JP et al (2002) CD44 is required for two consecutive steps in HGF/c-Met signaling. Genes Dev 16:3074–3086
Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 133(4):704–715
Eterno V, Zambelli A, Pavesi L, Villani L, Zanini V, Petrolo G, Manera S, Tuscano A, Amato A (2014) Adipose-derived Mesenchymal Stem Cells (ASCs) may favour breast cancer recurrence via HGF/c-Met signaling. Oncotarget. 5(3):613–633
Jalili A, Shirvaikar N, Marquez-Curtis LA, Turner AR, Janowska-Wieczorek A (2010) The HGF/c-Met axis synergizes with G-CSF in the mobilization of hematopoietic stem/progenitor cells. Stem Cells Dev. 19(8):1143–1151
Rø TB, Holien T, Fagerli UM, Hov H, Misund K, Waage A, Sundan A, Holt RU, Børset M (2013) HGF and IGF-1 synergize with SDF-1α in promoting migration of myeloma cells by cooperative activation of p21-activated kinase. Exp Hematol. 41(7):646–655
(2016) Ziegler adipocytes enhance murine pancreatic cancer growth via a hepatocyte growth factor (HGF)-mediated mechanism. Int J Surg 28:179–184
Duong MN, Geneste A, Fallone F, Li X, Dumontet C, Muller C (2017) The fat and the bad: mature adipocytes, key actors in tumor progression and resistance. Oncotarget. 8(34):57622–57641
Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 315(26):1650–1659
Beilmann M, Vande Woude GF, Dienes HP et al (2000) Hepatocyte growth factor-stimulated invasiveness of monocytes. Blood 95:3964–3969
Galimi F, Cottone E, Vigna E et al (2001) Hepatocyte growth factor is a regulator of monocyte-macrophage function. J Immunol 166:1241–1247
Giannoni P, Cutrona G, Totero D (2017) Survival and immunosuppression induced by hepatocyte growth factor in chronic lymphocytic leukemia. Curr Mol Med. 17(1):24–33
Glodde N, Bald T, van den Boorn-Konijnenberg D, Nakamura K et al (2017) Reactive neutrophil responses dependent on the receptor tyrosine kinase c-MET limit cancer immunotherapy. Immunity 47(4):789–802.e9
Benkhoucha M, Molnarfi N, Schneiter G, Walker PR, Lalive PH (2013) The neurotrophic hepatocyte growth factor attenuates CD8+ cytotoxic T-lymphocyte activity. J Neuroinflammation 10:154
Benkhoucha M, Molnarfi N, Kaya G, Belnoue E, Bjarnadóttir K, Dietrich PY, Walker PR, Martinvalet D, Derouazi M, Lalive PH (2017 Sep) Identification of a novel population of highly cytotoxic c-Met-expressing CD8+ T lymphocytes. EMBO Rep. 18(9):1545–1558
Piskounova E, Agathocleous M, Murphy MM, Hu Z, Huddlestun SE, Zhao Z, Leitch AM, Johnson TM, DeBerardinis RJ, Morrison SJ (2015) Oxidative stress inhibits distant metastasis by human melanoma cells. Nature. 527(7577):186–191
Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2(6):442–454
Bertola A, Bonnafous S, Cormont M, Anty R, Tanti JF, Tran A, Le Marchand-Brustel Y, Gual P (2007) Hepatocyte growth factor induces glucose uptake in 3T3-L1 adipocytes through A Gab1/phosphatidylinositol 3-kinase/Glut4 pathway. J Biol Chem. 282(14):10325–10332
Lyssiotis CA, Kimmelman AC (2017) Metabolic interactions in the tumor microenvironment. Trends Cell Biol 27(11):863–875
Leung E, Cairns RA, Chaudary N, Vellanki RN, Kalliomaki T, Moriyama EH, Mujcic H, Wilson BC, Wouters BG, Hill R, Milosevic M (2017) Metabolic targeting of HIF-dependent glycolysis reduces lactate, increases oxygen consumption and enhances response to high-dose single-fraction radiotherapy in hypoxic solid tumors. BMC Cancer. 17(1):418
Kim JW, Tchernyshyov I, Semenza GL, Dang CV (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 3(3):177–185
Mira A, Morello V, Céspedes MV, Perera T, Comoglio PM, Mangues R, Michieli P (2017) Stroma-derived HGF drives metabolic adaptation of colorectal cancer to angiogenesis inhibitors. Oncotarget. 8(24):38193–38213
Apicella M, Giannoni E, Fiore S, Ferrari KJ, Fernández-Pérez D, Isella C, Granchi C, Minutolo F, Sottile A, Comoglio PM, Medico E, Pietrantonio F, Volante M, Pasini D, Chiarugi P, Giordano S, Corso S (2018) Increased lactate secretion by cancer cells sustains non-cell-autonomous adaptive resistance to MET and EGFR targeted therapies. Cell Metab 28(6):848–865.e6
O’Brien CA, Pollett A, Gallinger S et al (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110
Al-Hajj M, Wicha MS, Benito-Hernandez A et al (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100:3983–3988
Collins AT, Berry PA, Hyde C et al (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951
Wang Z, Ali S, Banerjee S et al (2013) Activated K-Ras and INK4a/Arf deficiency promote aggressiveness of pancreatic cancer by induction of EMT consistent with cancer stem cell phenotype. J Cell Physiol 228:556–562
Galli R, Binda E, Orfanelli U et al (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011–7021
Yan B, Jiang Z, Cheng L, Chen K, Zhou C, Sun L, Qian W, Li J, Cao J, Xu Q, Ma Q, Lei J (2018) Paracrine HGF/c-MET enhances the stem cell-like potential and glycolysis of pancreatic cancer cells via activation of YAP/HIF-1α. Exp Cell Res. 371(1):63–71
Vermeulen L, De Sousa E, Melo F, van der Heijden M, Cameron K, de Jong JH, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, Sprick MR, Kemper K, Richel DJ, Stassi G, Medema JP (2010) Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol 12:468–476
Previdi S et al (2010) Interaction between human-breast cancer metastasis and bone microenvironment through activated hepatocyte growth factor/Met and β-catenin/Wnt pathways. Eur J Cancer 46:1679–1691
Lau EY, Lo J, Cheng BY, Ma MK, Lee JM, Ng JK, Chai S, Lin CH, Tsang SY, Ma S, Ng IO, Lee TK (2016) Cancer-associated fibroblasts regulate tumor-initiating cell plasticity in hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling. Cell Rep. 15(6):1175–1189
Abounader R, Laterra J (2005) Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro Oncol 7:436–451
Pennacchietti S, Michieli P, Galluzzo M et al (2003) Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3:347–361
Hara S, Nakashiro K, Klosek SK et al (2006) Hypoxia enhances c-Met/HGF receptor expression and signaling by activating HIF-1alpha in human salivary gland cancer cells. Oral Oncol 42:593–598
Ponzo MG, Lesurf R, Petkiewicz S et al (2009) Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer. Proc Natl Acad Sci U S A 106:12903–12908
Li Y, Lal B, Kwon S, Fan X, Saldanha U, Reznik TE, Kuchner EB, Eberhart C, Laterra J, Abounader R (2005) The scatter factor/hepatocyte growth factor: c-met pathway in human embryonal central nervous system tumor malignancy. Cancer Res 15;65(20):9355–9362
Xing F, Liu Y, Sharma S, Wu K, Chan MD, Lo HW, Carpenter RL, Metheny-Barlow LJ, Zhou X, Qasem SA, Pasche B, Watabe K (2016) Activation of the c-Met pathway mobilizes an inflammatory network in the brain microenvironment to promote brain metastasis of breast cancer. Cancer Res. 76(17):4970–4980
Zhang YW, Su Y, Volpert OV et al (2003) Hepatocyte growth factor/scatter factor mediates angiogenesis through positive VEGF and negative thrombospondin 1 regulation. Proc Natl Acad Sci U S A 100:12718–12723
Michieli P, Mazzone M, Basilico C et al (2004) Targeting the tumor and its microenvironment by a dual-function decoy Met receptor. Cancer Cell 6:61–73
Silvagno F, Follenzi A, Arese M et al (1995) In vivo activation of met tyrosine kinase by heterodimeric hepatocyte growth factor molecule promotes angiogenesis. Arterioscler Thromb Vasc Biol 15:1857–1865
(2017) Leung Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway. Oncogene 36:2680–2692
Sims DE (1986) The pericyte-a review. Tissue Cell 18(2):153–174
Ribatti D, Nico B, Crivellato E (2011) The role of pericytes in angiogenesis. Int J Develop Biol 55(3):261–268
Paiva AE, Lousado L, Guerra DAP et al (2018) Pericytes in the Premetastatic Niche. Cancer Res 78(11):2779–2787
Cao Y, Zhang ZL, Zhou M et al (2013) Pericyte coverage of differentiated vessels inside tumor vasculature is an independent unfavorable prognostic factor for patients with clear cell renal cell carcinoma. Cancer 119(2):313–334
Yonenaga Y, Mori A, Onodera H et al (2005) Absence of smooth muscle actin-positive pericyte coverage of tumor vessels correlates with hematogenous metastasis and prognosis of colorectal cancer patients. Oncology 69(2):159–166
O’Keeffe MB, Devlin AH, Burns AJ et al (2008) Investigation of pericytes, hypoxia, and vascularity in bladder tumors: association with clinical outcomes. Oncol Res 17(3):93–101
Xian X, Håkansson J, Ståhlberg A et al (2006) Pericytes limit tumor cell metastasis. J Clin Investig 116(3):642–651
Birbrair A, Zhang T, Wang ZM et al (2013) Skeletal muscle pericyte subtypes differ in their differentiation potential. Stem Cell Res 10(1):67–84
Birbrair A, Zhang T, Wang Z et al (2014) Type-2 pericytes participate in normal and tumoral angiogenesis. Am J Physiol Cell Physiol 307:C25–C38
Cooke VG, LeBleu VS, Keskin D et al (2012) Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway. Cancer Cell 21(1):66–81
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Zambelli, A., Biamonti, G., Amato, A. (2021). HGF/c-Met Signalling in the Tumor Microenvironment. In: Birbrair, A. (eds) Tumor Microenvironment. Advances in Experimental Medicine and Biology, vol 1270. Springer, Cham. https://doi.org/10.1007/978-3-030-47189-7_2
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