IHH and osteosarcoma: On the other hand, abnormal gene expression, including abnormal expression of TP53, Rb, C-MYC, IHH, and KRAS, can facilitate the reprogramming of MSCs into osteosarcoma cells.199,202–205 Notably, MSCs can also transform into tumor-associated fibroblasts (CAFs) after exposure to osteosarcoma cells, which can obviously promote osteosarcoma cell proliferation and metastasis.200,206 This process usually involves multiple substances, including monocyte chemotactic protein 1, growth-related oncogene-α, TGF-β, and intercellular adhesion factor.