%0 Journal Article
%T The role of PDGF in radiation oncology
%A Minglun Li
%A Verena Jendrossek
%A Claus Belka
%J Radiation Oncology
%D 2007
%I BioMed Central
%R 10.1186/1748-717x-2-5
%X PDGF was originally identified as a constituent of whole blood serum that was absent in cell-free plasma [1,2] and subsequently purified from human platelets [3,4]. Although the ¦Á-granules of platelets are a major storage site for PDGF, recent studies have shown that PDGF can be synthesized by a number of different cell types such as macrophages, epithelial and endothelial cells [5-8]. Studies have shown that PDGF has important physiologic functions in organ development [9,10]. PDGF has also been implicated in a wide variety of pathological processes, including fibrosis, atherosclerosis, glomerulonephritis and aggressive fibromatosis [11-15]. Moreover, aberrant production of PDGF and autocrine stimulation may be an important mechanism in the neoplastic conversion of PDGF receptor-positive cells [16-18]. Here, we point out the most important features of PDGF and PDGF receptors concerning their roles in radiation oncology.PDGF is a disulfide-linked dimer of two related polypeptide chains, designated A, B, C and D, which are assembled as heterodimers (PDGF-AB) or homodimers (PDGF-AA, PDGF-BB, PDGF-CC and PDGF-DD) [19-21]. PDGF exerts its biological activity by binding to structurally similar PDGF receptors (PDGFR-¦Á and -¦Â). The PDGFR-¦Á binds to A-, B- and C- chains with high affinity, whereas PDGFR-¦Â only binds the B- and D- chains [22-25]. Different from PDGF-A and -B, PDGF-C and PDGF-D require proteolytic activation before binding to and activation of PDGFR [19,20]. PDGF ligand dimer induces dimerization of both receptors and subsequently autophosphorylation of the PDGF receptor tyrosine kinase (RTK). Activated RTK phosphorylates numerous signaling molecules that initiate intracellular signaling cascades (Reviewed in Ref. [31]).The best characterized mechanisms by which PDGF down-streaming signaling mediates cellular responses involve the activation of the ras/MAPK pathway, which can functionally increase cellular proliferation, migration and differentiation [26], an
%U http://www.ro-journal.com/content/2/1/5