Role of growth factors and their receptors in proliferation of microvascular endothelial cells

Abstract

Investigations over the last decade have established the essential role of growth factors and their receptors during angiogenesis. The biological significance of VEGF, EGF, and bFGF is mediated by their receptors, which belong to the family of tyrosine kinase receptors: Flt-1 (VEGFR-1), KDR (VEGFR-2), EGFR, FGFR-1, FGFR-2, FGFR-3, and FGFR-4. Deeper understanding of the mechanism of activation of these growth factor receptors has allowed the development of a new pharmacological strategy aimed at controlling cancer cell proliferation. The results of a large body of preclinical as well as early clinical studies conducted suggest that targeting the growth factor receptors could represent a significant contribution to cancer therapy.

Simultaneous Blockade of Platelet-Derived Growth Factor-Receptor and Epidermal Growth Factor-Receptor Signaling and Systemic Administration of Paclitaxel as Therapy for Human Prostate Cancer Metastasis in Bone of Nude Mice

“…The roles of EGF and PDGF in angiogenesis have been reported for several human tumors (75)(76)(77)(78), and destruction of the vasculature within neoplasms can produce necrosis of actively growing tumors (79,80). The induction of apoptosis in tumor-associated endothelial cells suggests that this regimen of therapy is directed against tumor vasculature.…”

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells

“…It is well recognized that EGF and TGFa are among the most potent growth factors (Wells, 1999;Jorissen et al, 2003;Suhardja and Hoffman, 2003), which, by engaging the EGF receptor (EGFR), transmits signals for growth, survival, and, in some cases, motility (Misra and Pizzo, 1998;Price et al, 1999;Tsang and Crowe, 1999;Yart et al, 2001). Overexpression of EGF receptor is common among human epithelial malignancies (Merlino et al, 1985;Derynck et al, 1987;Costa et al, 1988;Sainsbury et al, 1988;Kikuchi et al, 1990;Ibrahim et al, 1997).…”

Soluble vascular endothelial growth factor receptor 1, and not receptor 2, is an independent prognostic factor in acute myeloid leukemia and myelodysplastic syndromes

“…6 The mitogenic effect of VEGF appears to be mediated by mitogen-activated protein kinase 7 and phosphatidylinositol 3-kinase, 8 which then stimulates the activation of intranuclear proteins such as cyclin D1 and induces progression of the cell cycle from the G 1 phase to the S-phase. 9,10 Neovascularization is required for tumor growth and metastasis. 11,12 Increased angiogenesis and tumor vascularity have been reported in both solid tumors and hematologic neoplasms.…”