Vascular changes in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most vascular solid tumors, in which angiogenesis plays an important role. The status of angiogenesis in HCC correlates with the disease progression and prognosis, and thus provides a potential therapeutic target. This review summarizes the vascular changes and molecular and cellular basis of angiogenesis in HCC. Development of HCC is characterized by arterialization of its blood supply and sinusoidal capillarization. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays a critical role in mediating angiogenesis in HCC. The VEGF can function on various types of cells, such as endothelial cells, hepatic stellate cells, endothelial progenitor cells and hemangiocytes, to induce vascular changes in HCC. Therefore, blockade of VEGF-mediated pathways, either by anti-VEGF neutralizing antibody or tyrosine kinase inhibitors that target VEGF receptors, suppresses carcinogenesis and angiogenesis in HCC. In addition to VEGF, several other angiogenic factors in HCC have recently been identified. These factors can also regulate angiogenic processes through interaction with VEGF or VEGF-independent pathways. Despite the fact that treatment of HCC remains a tough task due to lack of effective systemic therapy, antiangiogenic therapy has already entered clinical trials in HCC patients and sheds light on a promising novel treatment for this disease.
Yang
Zhen Fan
ZF
Centre for Cancer Research, Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
Poon
Ronnie T P
RT
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D042682:Angiopoietins / Q000502:physiology; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D004815:Epidermal Growth Factor / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology*; D008833:Microcirculation / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology; D009389:Neovascularization, Pathologic; D013939:Thymidine Phosphorylase / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D020533:Angiogenesis Inhibitors; D042682:Angiopoietins; D042461:Vascular Endothelial Growth Factor A; D004815:Epidermal Growth Factor; D013939:Thymidine Phosphorylase