Angiogenesis in hepatocellular carcinoma: the retrospectives and perspectives

Abstract

Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. Many angiogenic factors have been studied in HCC, and several anti-angiogenic therapies have been tested in animal models and patients. This paper summarizes the latest findings, especially regarding the clinical significance of endothelial cell markers and angiogenic factors in HCC, and experimental and clinical anti-angiogenesis therapies. Further developments in this area, such as endothelial cell-oriented research and better experimental and clinical designs in the evaluation of anti-angiogenic therapies are discussed.

Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis

“…Angiogenesis, defined as the formation of new blood vessels from existing vasculature, is an important process regulating the growth and development of malignancies including HCC (Sun and Tang, 2004;Pang and Poon, 2006). The extensive hypervascularity associated with HCC is thought to be driven in part by the proangiogenic factor known as vascular endothelial growth factor (VEGF) (Sun and Tang, 2004;Pang and Poon, 2006).…”

“…The extensive hypervascularity associated with HCC is thought to be driven in part by the proangiogenic factor known as vascular endothelial growth factor (VEGF) (Sun and Tang, 2004;Pang and Poon, 2006). Furthermore, the invasiveness of certain HCC lesions has recently been linked to high levels of VEGF, leading several authors to conclude that an important relationship between VEGF and prognosis exists for HCC (Li et al, 1998;Kanda et al, 2008).…”

“…This may be related to differences in the methods of measuring and reporting quantitative VEGF measurements. The three most commonly used methods are serum-based VEGF quantitation using enzymelinked immunosorbent assay, tissue-based semi-quantitative VEGF immunohistochemistry, and tissue-based mRNA measurement (Sun and Tang, 2004). One argument against the use of serum VEGF is the confounding role of platelets, which have been reported to release VEGF into the blood (Banks et al, 1998;Webb et al, 1998).…”

Combined endostatin/sFlt‐1 antiangiogenic gene therapy is highly effective in a rat model of HCC†

“…As in many other tumor entities, VEGF is also considered to be the most important proangiogenic factor in HCC. 10,11 Therefore, inhibition of this key regulator of HCC angiogenesis is the aim of approaches such as the use of small molecule inhibitors, monoclonal antibodies, or the so-called VEGF trap. 12 Expression of a soluble form of VEGF receptor 1 (sFlt-1) as a competitive VEGF inhibitor has been shown to inhibit tumor growth in different tumor models.…”

Genetic and epigenetic inactivation of T‐cadherin in human hepatocellular carcinoma cells

“…HCC is typically a hypervascular tumor. 14 Recent investigations have found that T-cadherin was overexpressed in intratumoral endothelial cells and played positive roles in angiogenesis of HCC. 15,16 However, the expression status and roles of T-cadherin in HCC cells or hepatocytes remain unclear.…”