Vascular Endothelial Growth Factor in ThyroidCancers.

Vascular endothelial growth factor (VEGF) is an essential peptide in new vessel growth in physiology(endometrial growth, embryonic development); pathological conditions (diabetic retinopathy, rheumatoidarthritis); as well as in tumor cell growth, particularly distant metastases. This study focused on VEGFstructure, receptors, and angiogensis in tumors, especially their roles in thyroid cancer. The VEGF mRNAundergoes alternative splicing events that generate four homodimeric isoforms, including VEGF121,VEGF165, VEGF189, or VEGF206. Using VEGF purified from a culture medium conditioned by A-431human epidermoid carcinoma cells, VEGF-binding site complexes of 230, 170, and 125 kDa were detectedon human umbilical vein endothelial cells. The VEGF specifically induced the tyrosine phosphorylationof a 190-kDa polypeptide, which had similar mass to the largest binding site detected throughaffinity cross-linking. A transmembrane receptor belongs to the tyrosine kinase family, fms-like tyrosinekinase (FLT). These receptor tyrosine kinases encoded by the FLT gene family have distinct functions inregulating blood vessel growth and differentiation. Regulation of VEGF is a complex, multistep mechanismin various kinds of cells and tissues. Hypoxia-dependent and -independent mechanisms are illustratedin different cancer tissues. Hypoxic tumor cells may switch to a proangiogenic phenotype, whichincreases VEGF transcription. Clinical applications of VEGF in cancer have included diagnosis, predictionof prognosis, and treatment in different solid tumors, including thyroid tumors. Studies involving thyroidcancer cell lines, serum level determination, immunohistocytochemical staining, molecular biologicalstudies, and gene therapy to the in vivo clinical trials, have shown that antiangiogensis therapy canprovide another treatment modality for thyroid cancer. Future studies focused on recombinant humananti-VEGF research involving patients with advanced thyroid cancer, and investigation of the protectionof high-risk patients by using novel antiangiogenic vaccines, are warranted. [ABSTRACT FROM AUTHOR]