Bone marrow cells: Important role on neovascularization of hepatocellular carcinoma

Present antivascular therapies including embolization to hepatocellular carcinoma (HCC) were not as satisfying as expected. The aim was to explore whether or not bone marrow cells (BMCs) played an important role on neovascularization in HCC.

Bone marrow-GFP(+) orthotropic HCC mice model was used. In controls and HCC mice, the dynamic change of circulating BMCs and serum vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) were measured by flow cytometry and enzyme linked immunosorbent assay, respectively. Intrahepatic distribution of BMCs was evaluated using immunofluorescent and realtime polymerase chain reaction protocols. BMCs' intrahepatic differentiation and proportion in vessels was investigated by immunofluorescent methods. Immunohistochemistry and western blotting were performed to examine the expression of adhesion molecule in tumor tissues and tumor free tissues.

Compared with controls, the frequency of circulating BMCs and serum VEGF, PDGF were much higher in HCC mice. The number of BMCs and the level of CD133 gene in tumor increased significantly relative to the tumor free zone. Since the early stage of HCC, BMCs have been mobilized, recruited into tumor and incorporated into different types of vessels of the liver. Besides into endothelial cells, BMCs also differentiated into vascular fibroblast and hepatic stellate cells. Moreover with tumor growth, the proportion of BMCs in vessels increased gradually.

Mobilized BMCs played an important role in tumor vasculogenesis of HCC. Combined blockading of bone marrow-mediated vasculogenesis may improve the efficacy of current therapy to HCC patients.