THBS1 and osteosarcoma: However, TSP-1 can also exert pro-metastatic effects as evidenced in breast cancer cells in vitro (158) and in osteosarcoma patients, in which both lung metastatic primary tumors and lung metastases expressed higher levels of TSP-1 in response to TGF-β, inducing further ECM remodeling by promoting MMP-2, MMP-9, and FN1 (159).