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Involvement of platelet‐derived growth factor ligands and receptors in tumorigenesis
Author(s) -
Heldin C.H.,
Lennartsson J.,
Westermark B.
Publication year - 2018
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12690
Subject(s) - platelet derived growth factor receptor , autocrine signalling , cancer research , platelet derived growth factor , angiogenesis , receptor , growth factor , stromal cell , growth factor receptor , biology , microbiology and biotechnology , medicine , signal transduction
Platelet‐derived growth factor ( PDGF ) isoforms and their receptors have important roles during embryogenesis, particularly in the development of various mesenchymal cell types in different organs. In the adult, PDGF stimulates wound healing and regulates tissue homeostasis. However, overactivity of PDGF signalling is associated with malignancies and other diseases characterized by excessive cell proliferation, such as fibrotic conditions and atherosclerosis. In certain tumours, genetic or epigenetic alterations of the genes for PDGF ligands and receptors drive tumour cell proliferation and survival. Examples include the rare skin tumour dermatofibrosarcoma protuberance, which is driven by autocrine PDGF stimulation due to translocation of a PDGF gene, and certain gastrointestinal stromal tumours and leukaemias, which are driven by constitute activation of PDGF receptors due to point mutations and formation of fusion proteins of the receptors, respectively. Moreover, PDGF stimulates cells in tumour stroma and promotes angiogenesis as well as the development of cancer‐associated fibroblasts, both of which promote tumour progression. Inhibitors of PDGF signalling may thus be of clinical usefulness in the treatment of certain tumours.