In vivo transplantation of endothelial cells derived from stem cells inhibits breast tumor growth and expression of tumor VEGFR2 and c-Myc

Introduction & Aim: Proliferation and invasion of breast tumor can be associated to activation of oncogenes, suppression of tumor suppressor genes and abnormal angiogenesis. c-Myc oncogene can act as a regulating factor in tumor progression and angiogenesis. Stem cell therapy is a new targeted therapy approach to control breast tumor growth in animal models. The aim of this study was to examine the response of breast tumors to exogenous endothelial cells with angiogenesis potential, with emphasize on VEGF2 and c-Myc expression. Methods: Mesenchymal stem cells (MSCs) isolated from mice bone marrow were induced to endothelial cells in a selective culture media. Besides, a syngeneic mouse model of breast carcinoma was developed after transplantation of 4T1 malignant cell line in the mice flank. The mice were then treated with induced endothelial cells by intra tumor route (1.5×106 cells/100 µl PBS). The response of tumors was examined after 30 days. A group of mice induced with tumors but untreated with active endothelial cells was considered as control. Tumor growth, histopathological parameters were undertaken. Tissue mRNA was analyzed for changes in c-Myc and VEGFR2 using real time PCR. Results: Mice treated with endothelial cells showed that tumor growth was significantly inhibited compared to controls (60%). c-Myc and VEGFR2 expression in tumors of mice treated with endothelial cells was markedly down regulated (80%) as compared to control group.Conclusion: The outcome of stem cell derived endothelial cell-therapy to mice is inhibition of tumor growth which is associated with down regulation of VEGFR2 and c-Myc.