Hypoxia-induced angiogenesis in human hepatocellular carcinoma.
Hepatocellular carcinoma is a typical hypervascular tumor. Generally, hepatocellular carcinoma is developed through liver cirrhosis induced by chronic liver injury. This chronic injury leads to changes in the cellular property of the liver and subsequently causes fibrogenesis to demolish normal liver blood system. The catastrophe of the normal liver blood system leads to the shortage of blood circulation in the liver and causes hypoxia. Moreover, the increased cellularity due to highly proliferative tumor cells also induces local hypoxia inside hepatocellular carcinoma. Hypoxia can stimulate angiogenesis to support tumor growth by induction of angiogenic factors. Thus hypoxia may be a major cause of hypervasculature of hepatocellular carcinoma. Recently it has been reported that several hypoxia-regulatory factors are closely involved in angiogenesis of hepatocellular carcinoma. The stability and function of these factors can be regulated by interaction with other protein factors and consequently modulate the expression of angiogenic factors depending on oxygen tension. Therefore induction mechanism of hypoxia and the role of hypoxia-regulatory factors could provide new insights into hepatocarcinogenesis and the treatment of hepatocellular carcinoma.
Kim
Kwang-Rok
KR
Angiogenesis Research Laboratory, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. qwonkim@plaza.snu.ac.kr
Moon
Hyo-Eun
HE
Kim
Kyu-Won
KW
D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology*; D008222:Lymphokines / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000821:virology; D010100:Oxygen / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D010100:Oxygen