Vascular endothelial growth factor in thyroid cancers.
Vascular endothelial growth factor (VEGF) is an essential peptide in new vessel growth in physiology (endometrial growth, embryonic development); pathological conditions (diabetic retinopathy, rheumatoid arthritis); as well as in tumor cell growth, particularly distant metastases. This study focused on VEGF structure, receptors, and angiogensis in tumors, especially their roles in thyroid cancer. The VEGF mRNA undergoes alternative splicing events that generate four homodimeric isoforms, including VEGF121, VEGF165, VEGF189, or VEGF206. Using VEGF purified from a culture medium conditioned by A-431 human epidermoid carcinoma cells, VEGF-binding site complexes of 230, 170, and 125 kDa were detected on human umbilical vein endothelial cells. The VEGF specifically induced the tyrosine phosphorylation of a 190-kDa polypeptide, which had similar mass to the largest binding site detected through affinity cross-linking. A transmembrane receptor belongs to the tyrosine kinase family, fms-like tyrosine kinase (FLT). These receptor tyrosine kinases encoded by the FLT gene family have distinct functions in regulating blood vessel growth and differentiation. Regulation of VEGF is a complex, multistep mechanism in various kinds of cells and tissues. Hypoxia-dependent and -independent mechanisms are illustrated in different cancer tissues. Hypoxic tumor cells may switch to a proangiogenic phenotype, which increases VEGF transcription. Clinical applications of VEGF in cancer have included diagnosis, prediction of prognosis, and treatment in different solid tumors, including thyroid tumors. Studies involving thyroid cancer cell lines, serum level determination, immunohistocytochemical staining, molecular biological studies, and gene therapy to the in vivo clinical trials, have shown that antiangiogensis therapy can provide another treatment modality for thyroid cancer. Future studies focused on recombinant human anti-VEGF research involving patients with advanced thyroid cancer, and investigation of the protection of high-risk patients by using novel antiangiogenic vaccines, are warranted.
Lin
Jen-Der
JD
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University, Taiwan, Republic of China. einjd@adm.cgmh.org.tw
Chao
Tzu-Chieh
TC
D017398:Alternative Splicing; D002455:Cell Division; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics*
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor