Bone marrow-derived lin-ckit+Sca-1+ stem cells do not contribute to vasculogenesis in Lewis lung carcinoma

The development of tumor vasculature is thought to occur through two complementary processes: sprout-ing angiogenesis from preexisting blood vessels of the host, and vasculogenesis, which involves the spon-taneous development of vessels through specific re-cruitment, differentiation, and vascular incorporation of circulating endothelial cells (EC), endothelial progeni-tor cells (EPC), or potentially bone marrow–derived cells. Recent reports, however, have challenged the belief that bone marrow–derived cells contribute to tumor neovascularization, claiming an exclusive role for sprouting angiogenesis in tumor blood vessel development. In the present study, we explored the recruitment behavior of bone marrow–derived lin–c-kit+Sca-1+ stem cells to subcutaneously implanted Lewis lung carcinoma in a syngeneic bone marrow transplantation model. We observed that although lin–c-kit+Sca-1+ and their derived cells demonstrate significant recruitment to carcinomas in vivo, they do not appear to functionally contribute to tumor neo-vascularization. Furthermore, our results support the hypothesis that new vessel formation in carcinomas occurs primarily through endothelialization from adja-cent and preexisting vasculature