Exogenous administration of tumor suppressor M, belonging to the IL‐6 cytokine family expressed in canine and human OS cells, promotes phosphorylation of STAT3 and upregulates Src and JAK2 activity, significantly increases VEGF expression in OS cells, and enhances OS neovascularization through STAT3‐specific inhibition of LLL3, which inhibited STAT3 activation and tumor angiogenesis induced by tumor suppressor M.121. The gene discussed is STAT3; the disease is neoplasm.