Role of Bone Marrow Derived Cells in the Development of Ewing´s Sarcoma

BOLONTRADE MARCELA F, ZHOU RONG R, ANDREEFF MICHAEL, WEIDNER DOUGLAS A, KLEINERMAN EUGENIE S

New Orleans, Louisiana

Simposio; American Association for Cancer Research (AACR); 2001

American Association for Cancer Research

Formation of new vessels that support tumor growth may involve vasculogenesis, as well as angiogenesis. Vascuogenesis, in contrast to angiogenesis, is the development of a vascular network from endothelial cell precursors. We investigated he role of bone marrow (BM) cells in the development of vessels and stroma of Ewing´s sarcomas. Human TC71 Ewing´s sarcoma cells form tumors 2 ½ weeks following injection into the bone. BM cells from mice with Ewing´s tumors and control mice were analyzed by FACS using UV excitation and dual-wavelength emission of cells stained with the dye Hoechst 33342. Side population (SP) cells were identified using this technique,which have been characterized as stem cells (Goodell et al, J Exp Med 1996; 183 (4):1797-906). The percentage of SP cells in the BM was significantly higher in tumor bearing mice than in controls (0.396 + 0.246% vs 0.045 + 0.035%, p=0.05). We further demonstrated that unfractionated BM cells stained with CMDiI were incorporated into the vasculature and surrounding stroma of developing Ewing´s tumors in vivo following i.v. injection. These data indicate that bone marrow cells are present in the tumor vasculature and stroma, which may contribute to the growth of Ewing´s sarcoma in mice. Furthermore, Ewing´s tumor cells may induce the bone marrow to produce cells to support the vasculogenesis needed by the growing tumor.