BOLONTRADE Marcela Fabiana
Role of bone marrow-derived side population cells in the development of Ewings sarcoma.
BOLONTRADE, MARCELA F.; WORTH, LAURA L.; ZHOU, RONG R.; MARINI, FRANK C.; ANDREEFF, MICHAEL; KLEINERMAN, EUGENIE S.
Stem Cell and Cell Therapy
Academy of Medical Sciences and Peking Union Medical College.
Año: 2003 vol. 1 p. 14 - 20
Objective: New vessel development is a key component in supporting the growth of solid tumors. Angiogenesis has been regarded as the sole mechanism by which vasculature develops, but a growing body of evidence has revealed that bone marrow (BM)-derived cells also contribute to new vessel growth in adult life. We have previously shown that BM-derived vessels are involved in formation of Ewings sarcoma vasculature. The purpose of this study was to determine if side population (SP) BM cells are, at least in part, responsible for this process. Methods: We used a bone marrow transplant (BMT) model to track SP-BM derived cells into Ewings sarcoma tumors growing in transplanted mice. Results and Conclusion: We found that BM SP cells, which have stem cell activity, are present in higher than normal frequencies in Ewings sarcoma-bearing mice. Mice transplanted with SP cells following lethal irradiation developed CD31-positive tumor neovessels that were in part derived from donor SP cells. Thus, SP cells were found to differentiate into non-hematopoietic cells that contributed to tumor vascular formation. This is the first report, to our knowledge, of the role of BM SP cells as direct contributors to development of tumor vessels. We conclude that vasculogenesis may play a role in Ewings sarcoma growth and development. These data suggest that genetically modified BM cells may provide a unique approach for the treatment of this disease.