In vivo trafficking of endothelial progenitor cells their possible involvement in the tumor neovascularization.

Circulating endothelial progenitor cell (EPCs) have been reported to contribute to vasculogenesis in adult organisms. To investigate the possible recruitment of EPCs and organization to form tumor vasculature, we investigated the in vivo real-time trafficking of EPCs non-invasively by using positron emission tomography (PET). A conditionally immortalized endothelial cell line derived from rat bone marrow (TR-BME1) was labeled with [2-(18)F] 2-fluoro-2-deoxy-D-glucose (FDG) and chased the accumulation in the rat tumor with PET. TR-BME1 cells were accumulated in the tumor tissues time-dependently. To investigate that the accumulation of the cells is specific or not, rats were previously irradiated with gamma-ray to suppress the influence of non-labeled EPCs derived from its bone marrow and used for PET analysis. The accumulation of TR-BME1 cells in the tumor was enhanced in gamma-ray-irradiated rats compared with that of non-irradiated ones, suggesting that TR-BME1 cells accumulated in the tumor specifically like as EPCs. Then the involvement of matrix metalloproteinases (MMPs) in EPC recruitment was examined. An inhibitor of MMP, MMI270, which suppressed invasion and tube formation abilities of TR-BME1 cells, only slightly suppressed the accumulation of TR-BME1 cells in the tumor of rats. These results suggest that EPCs are recruited in the tumor tissues for formation of tumor vasculature, and demonstrate the usefulness of TR-BME1 cells for studies on EPC related phenomena.