Transforming Growth Factor-β Signaling Plays a Pivotal Role in the Interplay Between Osteosarcoma Cells and Their Microenvironment.

摘要: Osteosarcomas are the most frequent form of primary bone tumors and mainly affect children, adolescents, young adults. Despite encouraging progress in therapeutic management, including advent multidrug chemotherapy, survival rates have remained unchanged for more than four decades: 75% at 5 years localized disease, but two groups patients still high risk: metastatic diagnosis (overall around 40% years) and/or poor responders to chemotherapy (20% years). Because these classified as " complex genomic, it is extremely difficult determine signaling pathways that might be targeted by specific therapies. A hypothesis has thus emerged, stating particular microenvironment may interfere with tumor cells promote chemoresistance dissemination metastases. The stroma composed a large number cell types (immune cells, endothelial mesenchymal stromal etc.) which secrete growth factors, such transforming factor-β (TGF-β), favors development metastases constituting permissive niche distant sites. Rather targeting themselves, very heterogeneous osteosarcoma, instead target key actors secreted microenvironment, TGF-βs, play part progression. In last decade, numerous studies shown overexpression TGF-β hallmark many cancers, tumors. this context, emerged crucial factor cross talk between poor-prognosis cancers. Secretion or can effectively act paracrine manner regulate phenotype functions stimulate protumorigenic microenvironmental changes. exert its function promoting angiogenesis, remodeling migration, inhibiting immu-nosurveillance. This review focuses on involvement development, related options possible