Osteosarcoma cells induce differentiation of mesenchymal stem cells into cancer associated fibroblasts through Notch and Akt signaling pathway.

Cancer-associated fibroblasts plays an important role in tumor progession, growth and metastasis. However, the mechanisms of mesenchymal stem cells differentiation to cancer-associated fibroblasts induced by tumor cells remains unclear. This study aimed to explore whether osteosarcoma cells can also induce BMSCs into CAFs through cells co-culture system, and identify the probably signailing pathway that mediates differentiation of BMSCs to CAFs. The results showed that osteosarcoma cells can induce BMSCs to exhibit the typical characteristics of CAFs, with increased expression of α-SMA, the most reliable marker for CAFs. Morever, we also reveals that Notch signaling acts upstream of Akt signaling in HBMSCs-TAFs differentiation.