Contribution of bone marrow derived cells to the development of the vasculature in Ewing´s sarcoma

BOLONTRADE MARCELA F, ZHOU RONG R, WORTH LAURA L, ANDREEFF MICHAEL, KLEINERMAN EUGENIE S

University of Texas MD Anderson Cancer Center

Jornada; UT MD Anderson Cancer Center Trainee Recognition Day; 2002

UT MD Anderson Cancer Center

Vasculogenesis –the process by which endothelial cell precursors are recruited and organized to form a vasculature- has traditionally been thought to play a role only in embryonic development. However, several studies suggest that vasculogenesis may also have a role in the formation of new vascular networks in adults, and that circulating endothelial precursor cells arise from outside of the vascular area. Using a mouse bone marrow transplantation model that takes advantage of major histocompatibility complex (MHC) haplotype differences between donor and recipient mice, we examined the contribution of donor bone marrow-derived cells to Ewing´s sarcoma neovascularization in recipient nude mice. We found that the donor bone marrow cells colocalized with neovessels in Ewing´s sarcomas in vivo. We also found that donor bone marrow-derived cells were involved in the formation of the tumor vasculature. Further, when a specific bone marrow subgroup of cells, termed Side Population (SP), is transplanted into mismatched MHC recipients, they contribute to the vasculature of Ewing´s sarcoma tumors in chimera mice. This population of cells, which exhibit the characteristics of stem cells, appear in higher frequencies in the bone marrow of tumor bearing mice compared with normal groups. When cultured under conditions that potentates the development of endothelial cells, the SP cells exhibit an endothelial-like cel phenotype. Our findings indicate that not only angiogenesis but also vasculogenesis is involved in the development of Ewing´s sarcoma in our mouse model. The identification of a population of cells in the bone marrow that can localize directly to the tumor area through chemotaxis and participate in tumor vasculogenesis opens the possibility of exploiting these cells for antitumor therapy and possibly gene therapy as well. Modulation of the vasculogenesis process may also provide new therapeutic targets.