The Endothelin Axis and Angiogenesis in Papillary Thyroid Carcinoma

Abstract

Papillary Thyroid Cancer (PTC) is the most common thyroid cancer accounting for 80% of all cases. The prognosis is good, with 5-year survival rates of 95%, but in some cases the tumour behaves in an aggressive manner characterized by local recurrence and/or metastasis, processes contributed to by angiogenesis. Angiogenesis is an essential physiologic activity involved in normal tissue biology and several pathologic conditions such as cardiac failure, and cancer. During carcinogenesis, tumour cells secrete pro-angiogenic factors to initiate angiogenesis. Angiogenesis also causes the migration of endothelial cells from pre-existing vessels to improve nutrient and oxygen delivery to tumours, angiogenesis has a key role in tumour growth and metastasis. Vascular endothelial growth factor (VEGF) has a pivotal role in the control of angiogenesis, aggressiveness in thyroid cancers. The endothelins (ETs) are a family of genes inducing DNA synthesis and cellular growth in different cells, affecting vascular tone and angiogenesis. ET-1 has a direct effect on neoplastic cells by inducing cellular proliferation, migration as well as invasion and inhibition of apoptosis. ET-1 induces VEGF expression by increasing hypoxia-inducible factor-1α (HIF-1α) stimulation.