Mesenchymal stromal cells belong to a diverse collection of cells in different states that are poorly characterized in non-epithelial tumors, such as sarcomas, and we identify IGFBP5 as an important factor being induced by tumor growth-suppressive mesenchymal stromal cells, and with a capacity to dampen sarcoma cell proliferation, induce caspase 3/7 activity, and support myogenic activity. The gene discussed is IGFBP5; the disease is sarcoma.