Reprogramming of non-malignant cells in saroma progression
Short background Cells of the tumor microenvironment control tumor growth, metastasis and treatment response. These aspects of tumor biology are well studied in tumors derived from epithelial cells, but less described in sarcomas. This study focuses on how stromal cells in pediatric rhabdomyosarcoma (RMS) are reprogrammed during sarcoma progression. RMSs are rare, heterogeneous soft tissue sarcomas recognized for their skeletal muscle differentiation status. Aims and objectives The overall aim is to identify useful biomarkers and characterize the crosstalk between stromal cells and RMS tumor cells to uncover pathways and mechanisms of potential therapeutic relevance. We aim to: 1. Characterize how RMS tumor cells reprogram stromal cells to lose their tumor suppressive functions during early tumor development 2. Characterize how tumor-naïve stromal cells suppress RMS tumor cell growth 3. Investigate whether oncogenic crosstalk between tumor cells and stromal cells is regulated by the PDGF, TGFbeta or IGF pathways |