Bone marrow stromal cells induce apoptosis of lymphoma cells in the presence of IFNgamma and TNF by producing nitric oxide

Bone marrow stromal cells (BMSCs) have been shown to promote the growth and survival of a wide variety of tumors. However, in the present study, we found that BMSCs induced apoptosis of lymphoma cells in the presence of INFγ and TNF. IFNγ and TNF dramatically induced the expression of inducible nitric oxide synthase (iNOS) by BMSCs in culture, and BMSCs generated from iNOS knockout mice did not induce apoptosis of lymphoma cells in the presence of IFNγ and TNF. In addition, we found that IFNγ and TNF also increased IL-6 expression by BMSCs, and anti-IL-6 further increased the killing of tumor cells by BMSCs. Taken together, our findings indicate that BMSCs induce apoptosis of lymphoma cells in the presence of IFNγ and TNF, and that the proapoptotic effect of BMSCs is mediated by nitric oxide. Our findings suggest a possibility to harness this proapoptotic feature of BMSCs for the development of novel therapeutic strategy to eliminate tumor cells, especially tumor cells in bone marrow.