A possible role of VEGF in osteolytic bone metastasis of hepatocellular carcinoma

The incidence of bone metastasis was around 13% in 404 patients with hepatocellular carcinoma (HCC) who underwent treatment at the National Kyushu Cancer Center between 1988-97, which is a high value among various cancers. This is, in part, due to the prolonged survival time of HCC patients in recent years. Serum vascular endothelial growth factor (VEGF) levels were significantly elevated in HCC patients with bone metastases as compared to those in patients with liver cirrhosis/chronic hepatitis and HCC patients without bone metastasis. VEGF was positively stained in both the primary lesion and bone metastasis of HCC by immunohistochemistry. In the process of bone metastasis, an increase in bone resorption is a crucial step prior to invasion of the bone. VEGF, the most important angiogenic factor, has been shown to stimulate bone resorption through its effects on osteoclasts. Thus, HCC cells reach the bone marrow space, and then secrete VEGF which facilitates osteolytic bone metastasis. VEGF may also facilitate tumor growth in the bone by acting as an angiogenic factor once invasion of the bone is complete. This might be another reason for the high incidence of bone metastasis in HCC.