Skip to main content Accessibility help
×
Hostname: page-component-68c7f8b79f-gnk9b Total loading time: 0 Render date: 2025-12-30T11:30:58.047Z Has data issue: false hasContentIssue false

13 - Platelet-derived growth factor

from Part 2.1 - Molecular pathways underlying carcinogenesis: signal transduction

Published online by Cambridge University Press:  05 February 2015

By
Arne Östman  and
Carl-Henrik Heldin
Edited by
Edward P. Gelmann ,
Charles L. Sawyers  and
Frank J. Rauscher, III
Arne Östman
Affiliation:
Cancer Center Karolinska, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Carl-Henrik Heldin
Affiliation:
Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
Edward P. Gelmann
Affiliation:
Columbia University, New York
Charles L. Sawyers
Affiliation:
Memorial Sloan-Kettering Cancer Center, New York
Frank J. Rauscher, III
Affiliation:
The Wistar Institute Cancer Centre, Philadelphia
Get access

Summary

Introduction

Platelet-derived growth factor (PDGF) constitutes a family of disulfide-linked dimeric growth factors that promote cell growth and migration by activation of tyrosine kinase PDGFα- and β-receptors (1). PDGFs act predominantly on mesenchymal cells, such as fibroblasts, pericytes, and smooth muscle cells, and are also potent regulators of glial cells. In the context of tumor biology, PDGF isoforms act as autocrine factors for malignant cells, and as stimulators of fibroblasts and pericytes in the tumor stroma. Clinical studies have validated PDGF receptors, expressed on malignant cells or on cells of the tumor stroma, as relevant cancer drug targets (2).

Structure of PDGF and PDGF receptors

PDGF is a family of disulfide-bounded homodimers of homologous A-, B-, C-, and D-polypeptide chains. In addition, the A- and B-chains form a heterodimer PDGF-AB. The two subunits in the dimer are arranged in an anti-parallel manner, creating two symmetric receptor binding epitopes. The PDGF isoforms show sequence similarly to vascular endothelial cell growth factors (VEGFs). In addition, PDGFs, VEGFs, and transforming growth factor-β (TGF-β) show a similar folding with a cystine-knot structure (1).

Information

Type
Chapter
Information
Molecular Oncology
Causes of Cancer and Targets for Treatment
 , pp. 135 - 143
Publisher: Cambridge University Press
Print publication year: 2013

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Heldin, C-H, Östman, A, Rönnstrand, L. Signal transduction via platelet-derived growth factor receptors. Biochimica et Biophysica Acta 1998;1378:F79–113.
Östman, A, Heldin, C-H. PDGF receptors as targets in tumor treatment. In: Vande Woude GF, Klein F, Advances in Cancer Research, editors. New York: Academic Press; 2007: 247–74.
Fredriksson, L, Li, H, Eriksson, U. The PDGF family: four gene products form five dimeric isoforms. Cytokine Growth Factor Reviews 2004;15:197–204.CrossRef
Heldin, C-H, Eriksson, U, Östman, A. New members of the platelet-derived growth factor family of mitogens. Archives of Biochemistry and Biophysics 2002;398:284–90.CrossRef
Omura, T, Heldin, C-H, Östman, A. Immunoglobulin-like domain 4-mediated receptor-receptor interactions contribute to platelet-derived growth factor-induced receptor dimerization. Journal of Biological Chemistry 1997;272:12 676–82.CrossRefGoogle ScholarPubMed
Blume-Jensen, P, Hunter, T. Oncogenic kinase signalling. Nature 2001;411:355–65.CrossRef
Baxter, RM, Secrist, JP, Vaillancourt, RR, Kazlauskas, A. Full activation of the platelet-derived growth factor beta-receptor kinase involves multiple events. Journal of Biological Chemistry 1998;273:17 050–5.CrossRefGoogle ScholarPubMed
Irusta, PM, Luo, Y, Bakht, O, et al. Definition of an inhibitory juxtamembrane WW-like domain in the platelet-derived growth factor beta receptor. Journal of Biological Chemistry 2002;277:38 627–34.CrossRefGoogle ScholarPubMed
Chiara, F, Bishayee, S, Heldin, C-H, Demoulin, J-B. Autoinhibition of the platelet-derived growth factor β receptor tyrosine kinase by its C-terminal tail. Journal of Biological Chemistry 2004;279:19 732–8.CrossRefGoogle ScholarPubMed
Soubeyran, P, Kowanetz, K, Szymkiewicz, I, Langdon, WY, Dikic, I. Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors. Nature 2002;416:183–7.CrossRef
Karlsson, S, Kowanetz, K, Sandin, Å, et al. Loss of T-cell protein tyrosine phosphatase induces recycling of the platelet-derived growth factor (PDGF) β-receptor but not the PDGF α-receptor. Molecular Biology of the Cell 2006;17:4846–55.CrossRef
Hellberg, C, Schmees, C, Karlsson, S, Åhgren, A, Heldin, C-H. Activation of protein kinase C α is necessary for sorting the PDGF β-receptor to Rab4a-dependent recycling. Molecular Biology of the Cell 2009;20:2856–63.CrossRef
Eriksson, A, Siegbahn, A, Westermark, B, Heldin, C-H, Claesson-Welsh, L. PDGF α- and β-receptors activate unique and common signal transduction pathways. EMBO Journal 1992;11:543–50.
Andrae, J, Gallini, R, Betsholtz, C. Role of platelet-derived growth factors in physiology and medicine. Genes and Development 2008;22:1276–312.CrossRef
Hoch, RV, Soriano, P. Roles of PDGF in animal development. Development 2003;130:4769–84.CrossRef
Lindahl, P, Johansson, BR, Levéen, P, Betsholtz, C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 1997;277:242–5.CrossRef
Enge, M, Bjarnegard, M, Gerhardt, H, et al. Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy. EMBO Journal 2002;21:4307–16.CrossRef
Abramsson, A, Kurup, S, Busse, M, et al. Defective N-sulfation of heparan sulfate proteoglycans limits PDGF-BB binding and pericyte recruitment in vascular development. Genes and Development 2007;21:316–31.CrossRef
Lindblom, P, Gerhardt, H, Liebner, S, et al. Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes and Development 2003;17:1835–40.CrossRef
Lindahl, P, Hellström, M, Kalén, M, et al. Paracrine PDGF-B/PDGF-Rbeta signaling controls mesangial cell development in kidney glomeruli. Development 1998;125:3313–22.
Boström, H, Willetts, K, Pekny, M, et al. PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis. Cell 1996;85:863–73.CrossRef
Karlsson, L, Lindahl, P, Heath, JK, Betsholtz, C. Abnormal gastrointestinal development in PDGF-A and PDGFR-α deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis. Development 2000;127:3457–66.
Gnessi, L, Basciani, S, Mariani, S, et al. Leydig cell loss and spermatogenic arrest in platelet-derived growth factor (PDGF)-A-deficient mice. Journal of Cell Biology 2000;149:1019–26.CrossRefGoogle ScholarPubMed
Karlsson, L, Bondjers, C, Betsholtz, C. Roles for PDGF-A and sonic hedgehog in development of mesenchymal components of the hair follicle. Development 1999;126:2611–21.
Soriano, P. The PDGF α-receptor is required for neural crest cell development and for normal patterning of the somites. Development 1997;124:2691–700.
Calver, AR, Hall, AC, Yu, WP, et al. Oligodendrocyte population dynamics and the role of PDGF in vivo. Neuron 1998;20:869–82.CrossRef
Fruttiger, M, Karlsson, L, Hall, AC, et al. Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice. Development 1999;126:457–67.
Gerhardt, H, Golding, M, Fruttiger, M, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. Journal of Cell Biology 2003;161:1163–77.CrossRefGoogle ScholarPubMed
Simon, M-P, Pedeutour, F, Sirvent, N, et al. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nature Genetics 1997;15:95–8.CrossRef
Shimizu, A, O’Brien, KP, Sjöblom, T, et al. The dermatofibrosarcoma protuberans-associated collagen type Iα1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Research 1999;59:3719–23.
Sjöblom, T, Shimizu, A, O’Brien, KP, et al. Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. Cancer Research 2001;61:5778–83.
Malhotra, B, Schuetze, SM. Dermatofibrosarcoma protuberans treatment with platelet-derived growth factor receptor inhibitor: a review of clinical trial results. Current Opinion in Oncology 2012;24:419–24.CrossRef
McArthur, GA. Dermatofibrosarcoma protuberans: a surgical disease with a molecular savior. Current Opinion in Oncology 2006;18:341–6.CrossRef
Heinrich, MC, Corless, CL, Duensing, A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003;299:708–10.CrossRef
Corless, CL, Schroeder, A, Griffith, D, et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. Journal of Clinical Oncology 2005;23:5357–64.CrossRefGoogle ScholarPubMed
Golub, TR, Barker, GF, Lovett, M, Gilliland, DG. Fusion of PDGF receptor β to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 1994;77:307–16.CrossRef
Carroll, M, Tomasson, MH, Barker, GF, Golub, TR, Gilliland, DG. The TEL/platelet-derived growth factor beta receptor (PDGF beta R) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGF beta R kinase-dependent signaling pathways. Proceedings of the National Academy of Sciences USA 1996;93:14 845–50.
Jousset, C, Carron, C, Boureux, A, et al. A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFRβ oncoprotein. EMBO Journal 1997;16:69–82.CrossRef
Apperley, JF, Gardembas, M, Melo, JV, et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. New England Journal of Medicine 2002;347:481–7.CrossRefGoogle ScholarPubMed
Cools, J, DeAngelo, DJ, Gotlib, J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. New England Journal of Medicine 2003;348:1201–14.CrossRefGoogle ScholarPubMed
Jones, AV, Cross, NC. Oncogenic derivatives of platelet-derived growth factor receptors. Cellular and Molecular Life Sciences 2004;61:2912–23.
Brennan, C, Momota, H, Hambardzumyan, D, et al. Glioblastoma subclasses can be defined by activity among signal transduction pathways and associated genomic alterations. PLoS One 2009;4:e7752.
Joensuu, H, Puputti, M, Sihto, H, Tynninen, O, Nupponen, NN. Amplification of genes encoding KIT, PDGFRalpha and VEGFR2 receptor tyrosine kinases is frequent in glioblastoma multiforme. Journal of Pathology 2005;207:224–31.CrossRefGoogle ScholarPubMed
Puputti, M, Tynninen, O, Sihto, H, et al. Amplification of KIT, PDGFRA, VEGFR2, and EGFR in gliomas. Molecular Cancer Research 2006;4:927–34.CrossRef
Verhaak, RG, Hoadley, KA, Purdom, E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17:98–110.CrossRef
Hermanson, M, Funa, K, Hartman, M, et al. Platelet-derived growth factor and its receptors in human glioma tissue: Expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Research 1992;52:3213–19.
Lokker, NA, Sullivan, CM, Hollenbach, SJ, Israel, MA, Giese, NA. Platelet-derived growth factor (PDGF) autocrine signaling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands may play a role in the development of brain tumors. Cancer Research 2002;62:3729–35.
Dresemann, G, Weller, M, Rosenthal, MA, et al. Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide. Journal of Neurooncology 2010;96:393–402.CrossRefGoogle ScholarPubMed
Reardon, DA, Dresemann, G, Taillibert, S, et al. Multicentre Phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma. British Journal of Cancer 2009;101:1995–2004.CrossRefGoogle ScholarPubMed
Paulsson, J, Lindh, MB, Jarvius, M, et al. Prognostic but not predictive role of platelet-derived growth factor receptors in patients with recurrent glioblastoma. International Journal of Cancer 2011;128:1981–8.CrossRefGoogle Scholar
Nupponen, NN, Paulsson, J, Jeibmann, A, et al. Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas. Modern Pathology 2008;21:265–70.CrossRef
Tamborini, E, Miselli, F, Negri, T, et al. Molecular and biochemical analyses of platelet-derived growth factor receptor (PDGFR) B, PDGFRA, and KIT receptors in chordomas. Clinical Cancer Research 2006;12:6920–8.CrossRef
Stacchiotti, S, Longhi, A, Ferraresi, V, et al. Phase II study of imatinib in advanced chordoma. Journal of Clinical Oncology 2012;30:914–20.CrossRefGoogle ScholarPubMed
Sundberg, C, Ljungström, M, Lindmark, G, Gerdin, B, Rubin, K. Microvascular pericytes express platelet-derived growth factor-β receptors in human healing wounds and colorectal adenocarcinoma. American Journal of Pathology 1993;143:1377–88.Google ScholarPubMed
Abramsson, A, Lindblom, P, Betsholtz, C. Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors. Journal of Clinical Investigation 2003;112:1142–51.CrossRefGoogle ScholarPubMed
Furuhashi, M, Sjöblom, T, Abramsson, A, et al. Platelet-derived growth factor production by B16 melanoma cells leads to increased pericyte abundance in tumors and an associated increase in tumor growth rate. Cancer Research 2004;64:2725–33.CrossRef
Guo, P, Hu, B, Gu, W, et al. Platelet-derived growth factor-B enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment. American Journal of Pathology 2003;162:1083–93.CrossRefGoogle ScholarPubMed
Lederle, W, Linde, N, Heusel, J, et al. Platelet-derived growth factor-B normalizes micromorphology and vessel function in vascular endothelial growth factor-A-induced squamous cell carcinomas. American Journal of Pathology 2010;176:981–94.CrossRefGoogle ScholarPubMed
Robinson, SP, Ludwig, C, Paulsson, J, Östman, A. The effects of tumor-derived platelet-derived growth factor on vascular morphology and function in vivo revealed by susceptibility MRI. International Journal of Cancer 2008;122:1548–56.CrossRefGoogle ScholarPubMed
Bergers, G, Song, S, Meyer-Morse, N, Bergsland, E, Hanahan, D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. Journal of Clinical Investigation 2003;111:1287–95.CrossRefGoogle ScholarPubMed
McCarty, MF, Somcio, RJ, Stoeltzing, O, et al. Overexpression of PDGF-BB decreases colorectal and pancreatic cancer growth by increasing tumor pericyte content. Journal of Clinical Investigation 2007;117:2114–22.CrossRefGoogle ScholarPubMed
Crawford, Y, Kasman, I, Yu, L, et al. PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell 2009;15:21–34.CrossRef
Östman, A, Augsten, M. Cancer-associated fibroblasts and tumor growth: bystanders turning into key players. Current Opinion in Genetic Development 2009;19:67–73.CrossRef
Hägglöf, C, Hammarsten, P, Josefsson, A, et al. Stromal PDGFRbeta expression in prostate tumors and non-malignant prostate tissue predicts prostate cancer survival. PLoS One 2010;5:e10747.
Paulsson, J, Sjöblom, T, Micke, P, et al. Prognostic significance of stromal platelet-derived growth factor β-receptor expression in human breast cancer. American Journal of Pathology 2009;175:334–41.CrossRefGoogle ScholarPubMed
Anderberg, C, Li, H, Fredriksson, L, et al. Paracrine signaling by platelet-derived growth factor-CC promotes tumor growth by recruitment of cancer-associated fibroblasts. Cancer Research 2009;69:369–78.CrossRef
Forsberg, K, Valyi-Nagy, I, Heldin, C-H, Herlyn, M, Westermark, B. Platelet-derived growth factor (PDGF) in oncogenesis: development of a vascular connective tissue stroma in xenotransplanted human melanoma producing PDGF-BB. Proceedings of the National Academy of Sciences USA 1993;90:393–7.CrossRef
Kitadai, Y, Sasaki, T, Kuwai, T, et al. Targeting the expression of platelet-derived growth factor receptor by reactive stroma inhibits growth and metastasis of human colon carcinoma. American Journal of Pathology 2006;169:2054–65.CrossRefGoogle ScholarPubMed
Murata, T, Mizushima, H, Chinen, I, et al. HB-EGF and PDGF mediate reciprocal interactions of carcinoma cells with cancer-associated fibroblasts to support progression of uterine cervical cancers. Cancer Research 2011;71:6633–42.CrossRef
Okada, H, Honda, M, Campbell, JS, et al. Acyclic retinoid targets platelet-derived growth factor signaling in the prevention of hepatic fibrosis and hepatocellular carcinoma development. Cancer Research 2012;72:4459–71.CrossRef
Pietras, K, Pahler, J, Bergers, G, Hanahan, D. Functions of paracrine PDGF signaling in the proangiogenic tumor stroma revealed by pharmacological targeting. PLoS Medicine 2008;5:e19.
Sumida, T, Kitadai, Y, Shinagawa, K, et al. Anti-stromal therapy with imatinib inhibits growth and metastasis of gastric carcinoma in an orthotopic nude mouse model. International Journal of Cancer 2011;128:2050–62.CrossRefGoogle Scholar
Bandapalli, OR, Macher-Goeppinger, S, Schirmacher, P, Brand, K. Paracrine signalling in colorectal liver metastases involving tumor cell-derived PDGF-C and hepatic stellate cell-derived PAK-2. Clinical and Experimental Metastasis 2012;29:409–17.CrossRef
Conley-LaComb, MK, Huang, W, Wang, S, et al. PTEN regulates PDGF ligand switch for beta-PDGFR signaling in prostate cancer. American Journal of Pathology 2012;180:1017–27.CrossRefGoogle ScholarPubMed
Najy, AJ, Jung, YS, Won, JJ, et al. Cediranib inhibits both the intraosseous growth of PDGF D-positive prostate cancer cells and the associated bone reaction. The Prostate 2012;72:1328–38.CrossRef
Prakash, J, de Jong, E, Post, E, et al. Targeting tumor stromal cells through a PDGF-β receptor binding carrier. Journal of Controlled Release 2010;148:e116.CrossRefGoogle ScholarPubMed
Falcon, BL, Pietras, K, Chou, J, et al. Increased vascular delivery and efficacy of chemotherapy after inhibition of platelet-derived growth factor-B. American Journal of Pathology 2011;178:2920–30.CrossRefGoogle ScholarPubMed
Pietras, K, Stumm, M, Hubert, M, et al. STI571 enhances the therapeutic index of epothilone B by a tumor-selective increase of drug uptake. Clinical Cancer Research 2003;9:3779–87.
Pietras, K, Östman, A, Sjöquist, M, et al. Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors. Cancer Research 2001;61:2929–34.
Laimer, D, Dolznig, H, Kollmann, K, et al. PDGFR blockade is a rational and effective therapy for NPM-ALK-driven lymphomas. Nature Medicine 2012;18:1699–704.CrossRef
Koos, B, Paulsson, J, Jarvius, M, et al. Platelet-derived growth factor receptor expression and activation in choroid plexus tumors. American Journal of Pathology 2009;175:1631–7.CrossRefGoogle ScholarPubMed
Cao, R, Björndahl, MA, Religa, P, et al. PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis. Cancer Cell 2004;6:333–45.CrossRef
Dolloff, NG, Shulby, SS, Nelson, AV, et al. Bone-metastatic potential of human prostate cancer cells correlates with Akt/PKB activation by alpha platelet-derived growth factor receptor. Oncogene 2005;24:6848–54.CrossRef
Gotzmann, J, Fischer, AN, Zojer, M, et al. A crucial function of PDGF in TGF-β-mediated cancer progression of hepatocytes. Oncogene 2006;25:3170–85.CrossRef
Jechlinger, M, Sommer, A, Moriggl, R, et al. Autocrine PDGFR signaling promotes mammary cancer metastasis. Journal of Clinical Investigation 2006;116:1561–70.CrossRefGoogle ScholarPubMed
Liu, J, Liao, S, Huang, Y, et al. PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer. Clinical Cancer Research 2011;17:3638–48.CrossRef
Russell, MR, Liu, Q, Lei, H, Kazlauskas, A, Fatatis, A. The α-receptor for platelet-derived growth factor confers bone-metastatic potential to prostate cancer cells by ligand- and dimerization-independent mechanisms. Cancer Research 2010;70:4195–203.CrossRef
Schito, L, Rey, S, Tafani, M, et al. Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells. Proceedings of the National Academy of Sciences USA 2012;109:E2707–16.
van Zijl, F, Mair, M, Csiszar, A, et al. Hepatic tumor-stroma crosstalk guides epithelial to mesenchymal transition at the tumor edge. Oncogene 2009;28:4022–33.CrossRef
Peña, C, Cespedes, MV, Bradic Lindh, M, et al. STC1 expression by cancer-associated fibroblasts drives metastasis of colorectal cancer. Cancer Research 2012;73:1287–97.CrossRef
Xue, Y, Lim, S, Yang, Y, et al. PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells. Nature Medicine 2012;18:100–10.CrossRef
Ding, W, Knox, TR, Tschumper, RC, et al. Platelet-derived growth factor (PDGF)-PDGF receptor interaction activates bone marrow-derived mesenchymal stromal cells derived from chronic lymphocytic leukemia: implications for an angiogenic switch. Blood 2010;116:2984–93.CrossRef
Shinagawa, K, Kitadai, Y, Tanaka, M, et al. Stroma-directed imatinib therapy impairs the tumor-promoting effect of bone marrow-derived mesenchymal stem cells in an orthotopic transplantation model of colon cancer. International Journal of Cancer 2013;132:813–23.CrossRefGoogle Scholar
Cooke, VG, LeBleu, VS, Keskin, D, et al. Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway. Cancer Cell 2012;21:66–81.CrossRef
Xian, X, Hakansson, J, Stahlberg, A, et al. Pericytes limit tumor cell metastasis. Journal of Clinical Investigation 2006;116:642–51.CrossRefGoogle ScholarPubMed

Accessibility standard: Unknown

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

Accessibility compliance for the PDF of this book is currently unknown and may be updated in the future.

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×