Gli2-Mediated Hedgehog Signaling in Sarcoma Development and Differentiation

Sarcomas are a rare family of tumors derived from mesenchymal tissues including bone, fat, cartilage, and muscle. Sarcomas vary significantly across histological and molecular subtypes, making them difficult to treat clinically. Due to the rare incidence of disease, sarcoma research is hindered by poor accumulation of tumor samples and model systems, making molecular mechanistic research difficult to achieve. Hedgehog signaling, and embryonic signaling pathway, has been implicated in mesenchymal differentiation and formation of a small number of sarcoma subtypes, however, its role has not been clearly established. Here we evaluate Gli2-mediated hedgehog signaling and its capacity to influence sarcoma development by evaluating its role in osteosarcoma induced bone remodeling, as well as, integrating bioinformatics data to identify themes of commonality across soft tissue sarcoma subtypes that might elucidate the biological function of Gli2 mediated hedgehog signaling in sarcomas. Lastly, we identified a striking trend of correlation relationships between Gli2 mRNA expression and antigen presentation and immune cell markers that suggests Gli2 may influence immune cell infiltration into soft tissue sarcoma tumors.