Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Nahyun Choi
  • Jung-Hun Moon
  • Jong-Hyuk SungEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101813


Historical Background

Platelet-derived growth factor, PDGF, was first found as a factor that comes from platelet that stimulates the growth of fibroblasts in vitro (Hannink and Donoghue 1989). Also, PDGF is characterized as a potent mitogen for mesenchymal origin cells such as smooth muscle cells, fibroblasts, and glial cells (Hannink and Donoghue 1989). Furthermore, it is known that PDGF is related to blood vessel formation and induces angiogenesis (Keck et al. 1989). Two types of PDGF polypeptides, PDGF-A and PDGF-B, were firstly reported for subtypes. In early 2000s, additional two types of PDGF were identified, which are PDGF-C and PDGF-D (Li et al. 2000; Bergsten et al. 2001). This entry examines further details of PDGF.

PDGF Receptor

PDGF receptor (PDGFR) is a cell surface receptor and type of receptor tyrosine kinase (RTK). After ligand binding, PDGFR internalizes and regulates downstream signaling such as Akt and ERK (Heldin 1992). Two...

This is a preview of subscription content, log in to check access.


  1. Akhavan D, Pourzia AL, Nourian AA, Williams KJ, Nathanson D, Babic I, Villa GR, Tanaka K, Nael A, Yang H, Dang J, Vinters HV, Yong WH, Flagg M, Tamanoi F, Sasayama T, James CD, Kornblum HI, Cloughesy TF, Cavenee WK, Bensinger SJ, Mischel PS. De-repression of PDGFRβ transcription promotes acquired resistance to EGFR tyrosine kinase inhibitors in glioblastoma patients. Cancer Discov. 2013;3(5):534–47.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alvarez RH, Kantarjian HM, Cortes JE. Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin Proc. 2006;81(9):1241–57.CrossRefPubMedGoogle Scholar
  3. Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008;22:1276–312.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Bergsten E, Uutela M, Li X, Pietras K, Ostman A, Heldin CH, Alitalo K, Eriksson U. PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat Cell Biol. 2001;3:512–6.CrossRefPubMedGoogle Scholar
  5. Bible KC, Suman VJ, Molina JR, Smallridge RC, Maples WJ, Menefee ME, Rubin J, Karlin N, Sideras K, Morris 3rd JC, McIver B, Hay I, Fatourechi V, Burton JK, Webster KP, Bieber C, Traynor AM, Flynn PJ, Cher Goh B, Isham CR, Harris P, Erlichman C. A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H. Endocrine Malignancies Disease Oriented Group, Mayo Clinic Cancer Center, and the Mayo Phase 2 Consortium. J Clin Endocrinol Metab. 2014;99(5):1687–93.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Buchdunger E, Zimmerman J, Mett H, Meyer T, Muller M, Druker BJ, Lydon NB. Inhibition of the Abl protein tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res. 1996;56:100–4.PubMedGoogle Scholar
  7. Chiorean EG, Sweeney C, Youssoufian H, Qin A, Dontabhaktuni A, Loizos N, Nippgen J, Amato R. A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRα) monoclonal antibody, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014;73(3):595–604.CrossRefPubMedGoogle Scholar
  8. Demoulin JB, Essaghir A. PDGF receptor signaling networks in normal and cancer cells. Cytokine Growth Factor Rev. 2014;25:273–83.CrossRefPubMedGoogle Scholar
  9. Duffy M. A new, innovative potential drug therapy in clinical trials for the treatment of wet macular degeneration. 2016. Available from http://www.visionaware.org/blog/visionaware-blog/a-potential-new-drug-therapy-in-clinical-trials-for-the-treatment-of-wet-macular-degeneration/12
  10. Hannink M, Donoghue DJ. Structure and function of platelet-derived growth factor (PDGF) and related proteins. Biochim Biophys Acta. 1989;989(1):1–10.PubMedGoogle Scholar
  11. Heldin CH. Structural and functional studies on platelet-derived growth factor. EMBO J. 1992;11(12):4251–9.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Heldin CH. Targeting the PDGF signaling pathway in tumor treatment. Cell Commun Signal. 2013;11:97.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Ho AL, Vasudeva SD, Laé M, Saito T, Barbashina V, Antonescu CR, Ladanyi M, Schwartz GK. PDGF receptor alpha is an alternative mediator of rapamycin-induced Akt activation: implications for combination targeted therapy of synovial sarcoma. Cancer Res. 2012;72(17):4515–25.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 1996;15(2):290–8.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science. 1989;246:1309–12.CrossRefPubMedGoogle Scholar
  16. Kim WS, Park HS, Sung JH. The pivotal role of PDGF and its receptor isoforms in adipose-derived stem cells. Histol Histopathol. 2015;30(7):793–9.PubMedGoogle Scholar
  17. Laimer D, Dolznig H, Kollmann K, Vesely PW, Schlederer M, Merkel O, Schiefer AI, Hassler MR, Heider S, Amenitsch L, Thallinger C, Staber PB, Simonitsch-Klupp I, Artaker M, Lagger S, Turner SD, Pileri S, Piccaluga PP, Valent P, Messana K, Landra I, Weichhart T, Knapp S, Shehata M, Todaro M, Sexl V, Höfler G, Piva R, Medico E, Ruggeri BA, Cheng M, Eferl R, Egger G, Penninger JM, Jaeger U, Moriggl R, Inghirami G, Kenner L. PDGFR blockade is a rational and effective therapy for NPM-ALK-driven lymphomas. Nat Med. 2012;18(11):1699–704.CrossRefPubMedGoogle Scholar
  18. Levitzki A. PDGF receptor kinase inhibitors for the treatment of pdgf driven diseases. Cytokine Growth Factor Rev. 2004;15:229–35.CrossRefPubMedGoogle Scholar
  19. Li X, Ponten A, Aase K, Karlsson L, Abramsson A, Uutela M, Backstrom G, Hellstrom M, Bostrom H, Li H, Soriano P, Betsholtz C, Heldin CH, Alitalo K, Ostman A, Eriksson U. PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. Nat Cell Biol. 2000;2:302–9.CrossRefPubMedGoogle Scholar
  20. Liu C, Li J, Xiang X, Guo L, Tu K, Liu Q, Shah VH, Kang N. PDGF receptor-α promotes TGF-β signaling in hepatic stellate cells via transcriptional and posttranscriptional regulation of TGF-β receptors. Am J Physiol Gastrointest Liver Physiol. 2014;307(7):G749–59.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Miyazaki H, Yoshimatsu Y, Akatsu Y, Mishima K, Fukayama M, Watabe T, Miyazono K. Expression of platelet-derived growth factor receptor β is maintained by Prox1 in lymphatic endothelial cells and is required for tumor lymphangiogenesis. Cancer Sci. 2014;105(9):1116–23.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. PNAS. 1996;93(6):2567–81.CrossRefGoogle Scholar
  23. Ophthotech. Fovista anti-PDGF therapy clinical development. 2016. Available from http://www.ophthotech.com/product-candidates/fovista/
  24. Pierce GF, Tarpley JE, Allman RM, Goode PS, Serdar CM, Morris B, Mustoe TA, Vande BJ. Tissue repair processes in healing chronic pressure ulcers treated with recombinant platelet-derived growth factor BB. Am J Pathol. 1994;145(6):1399–410.PubMedPubMedCentralGoogle Scholar
  25. Pietras K, Sjoblom T, Rubin K, Heldin C-H, Ostman A. PDGF receptors as cancer drug targets. Focus. 2003;3:439–43.Google Scholar
  26. Pinto MP, Dye WW, Jacobsen BM, Horwitz KB. Malignant stroma increases luminal breast cancer cell proliferation and angiogenesis through platelet-derived growth factor signaling. BMC Cancer. 2014;14:735.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Robson MC, Phillips LG, Thomason A, Robson LE, Pierce GF. Platelet-derived growth factor BB for the treatment of chronic pressure ulcers. Lancet. 1992;339:23–5.CrossRefPubMedGoogle Scholar
  28. Wang P, Song L, Ge H, Jin P, Jiang Y, Hu W, Geng N. Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo. Onco Targets Ther. 2014;7:1761–8.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Weissmueller S, Manchado E, Saborowski M, Morris 4th JP, Wagenblast E, Davis CA, Moon SH, Pfister NT, Tschaharganeh DF, Kitzing T, Aust D, Markert EK, Wu J, Grimmond SM, Pilarsky C, Prives C, Biankin AV, Lowe SW. Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor β signaling. Cell. 2014;157(2):382–94.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Yang W, Wetterskog D, Matsumoto Y, Funa K. Kinetics of repression by modified p53 on the PDGF beta-receptor promoter. Int J Cancer. 2008;123(9):2020–30.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.College of PharmacyYonsei UniversityIncheonKorea