Bone marrow derived cells participate in the formation of tumor vasculature in Ewing's sarcoma.

BOLONTRADE, MARCELA F.; WORTH, LAURA L.; MARINI, FRANK C.; ANDREEFF, MICHAEL; KLEINERMAN, EUGENIE S.

Philadelphia, Pennsylvania.

Simposio; 44to Encuentro y Exposición Anual. American Society of Hematology (ASH).; 2002

American Society of Hematology (ASH)

The 2 year metastases-free survival rate for patients with Ewing’s sarcoma has not improved over the past 15 years. Understanding the biology and mechanisms involved in Ewing’s sarcoma tumor growth and progression may lead to the identification of novel therapeutic approaches. New vessel development is a key component in supporting the growth of solid tumors. The purpose of this study was to determine the contribution of bone marrow (BM) endothelial precursor cells in the tumor neovascularization process. This was done using several strategies to track BM-derived cells. Fluorescent cell-tracking studies demonstrated that BM-derived cells colocalized with tumor neovessels. Using a BM transplant model that takes advantage of MHC differences between donors and recipients, we demonstrated that donor BM cells were involved in the formation of the tumor vasculature. These studies were confirmed using BM cells from transgenic LacZ mice, which migrated into the tumor neovascular area and also surrounding the tumor stroma in the transplanted mice. We have begun studies to determine which cell populations in the BM are responsible for this process. We hypothesized that BM side population cells (SP) were good candidates since they have stem cell activity. We therefore tested the ability of SP cells to contribute to neovascularization in Ewing's sarcoma using our MHC mismatched transplant model. Mice transplanted with SP cells following lethal irradiation developed tumor neovessels that were derived from the donor SP cells. Thus, SP cells not only replenished the hematopoietic system and rescued lethally irradiated mice, but also were found to differentiate into non-hematopoietic cells contributing to the formation of the tumor vasculature. In summary, we have demonstrated that BM-derived cells are involved in the generation of the new vasculature during the growth of Ewing’s sarcoma. We therefore conclude that vasculogenesis may play a role in Ewing's sarcoma growth and development. These data suggest that genetically modified BM cells may provide a unique approach for the treatment of this disease.