Pathological significance of vascular endothelial growth factor A isoform expression in human cancer.
Vascular endothelial growth factor (VEGF) is a highly specific factor for vascular endothelial cells. Five VEGF-A isoforms (splice variants 121, 145, 165, 189 and 206) are generated as a result of alternative splicing from a single VEGF-A gene. These differ in their molecular weights and in biological properties such as their ability to bind to cell-surface heparan sulfate proteoglycans. Deregulated VEGF-A expression contributes to the development of solid tumors by promoting tumor angiogenesis. More specifically, VEGF-A189 expression is related to angiogenesis and prognosis in certain human solid tumors. VEGF-A189 expression is also related to the xenotransplantability of human cancers into immunodeficient mice in vivo. Consequently, inhibition of VEGF-A or VEGF-A189 signaling regulates the development and metastasis of a variety of tumors. This review focuses on recent studies of the mechanisms by which VEGF-A regulates angiogenesis in the cancer stroma and on our recent findings concerning the potential mechanisms of VEGF-A189 expression on tumor growth and metastasis.
Nakamura
Masato
M
Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan. mnakamur@is.icc.u-tokai.ac.jp
Abe
Yoshiyuki
Y
Tokunaga
Tetsuji
T
D000818:Animals; D016228:Endothelial Growth Factors / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D020033:Protein Isoforms; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A
D016228:Endothelial Growth Factors; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D020794:Receptor Protein-Tyrosine Kinases