VEGF and cholangiocarcinoma: Feeding the tumor
The ability for cells to establish a functional and integrated vascular system is critical for proper tissue growth and cellular homeostasis. Blood vessels provide the essential nutrition and oxygen to cells, however the formation of new blood vessels can also trigger a detrimental and fatal pathway as tumor cells seek out nutritional support. Tumor vasculature and the angiogenic process provide malignant cells with the fuel that they need to spread, invade and metastasize into other organs. "Smart" tumors are able to develop their own blood supply via angiogenic sprouting and vessel formation. Vascular endothelial growth factor (VEGF) has been targeted as a critical regulator of new blood vessel formation (angiogenesis) in numerous cancers including the fatal biliary cancer, cholangiocarcinoma. Cholangiocarcinoma is a cancer of bile ducts or cholangiocytes that is difficult to diagnose and has limited treatment options. Cholangiocytes and cholangiocarcinoma tumors are nourished by the peribiliary plexus; a vascular bed that influences the regulation of cholangiocyte and cholangiocarcinoma response via VEGF expression. Due to its proximity to the vascular bed, cholangiocarcinoma has the ability to metastasize and therefore is regulated by its ability to activate angiogenesis. Besides VEGF, other growth factors contribute to the angiogenic process and can increase tumor proliferation and cholangiocarcinogenesis, however VEGF appears to be the most prominent factor involved in tumor regulation and angiogenesis. VEGF is regulated by VEGF receptor inhibitors or other signaling pathway inhibitors as well as by specific microRNAs that are able to alter VEGF receptor and protein expression. The aim of our review is to define angiogenesis and the formation of new blood vessels and highlight recent studies involving VEGF and cholangiocarcinoma along with new insights into microRNA regulation of VEGF during tumor growth and development. We will briefly touch on recent clinical studies involving VEGF and cholangiocarcinoma. In this concise review we hope to give the reader a better understanding of the importance of angiogenesis and cholangiocarcinoma tumor growth.