Xu Guangwu, Zhang Yingyu, Zhang Liying, Ren Guangwen, Shi Yufang
Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, 661 Hoes Lane, Piscataway, NJ 08854, USA.
Biochem Biophys Res Commun. 2008 Oct 31;375(4):666-70. doi: 10.1016/j.bbrc.2008.08.077. Epub 2008 Aug 26.
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 INFgamma and TNF. IFNgamma 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 IFNgamma and TNF. In addition, we found that IFNgamma 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 IFNgamma 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.
骨髓基质细胞（BMSCs）已被证明可促进多种肿瘤的生长和存活。然而，在本研究中，我们发现BMSCs在IFNγ和TNF存在的情况下可诱导淋巴瘤细胞凋亡。IFNγ和TNF显著诱导培养的BMSCs中诱导型一氧化氮合酶（iNOS）的表达，而来自iNOS基因敲除小鼠的BMSCs在IFNγ和TNF存在的情况下不会诱导淋巴瘤细胞凋亡。此外，我们发现IFNγ和TNF还可增加BMSCs的IL-6表达，抗IL-6进一步增强了BMSCs对肿瘤细胞的杀伤作用。综上所述，我们的研究结果表明，BMSCs在IFNγ和TNF存在的情况下可诱导淋巴瘤细胞凋亡，且BMSCs的促凋亡作用由一氧化氮介导。我们的研究结果提示，利用BMSCs的这种促凋亡特性开发消除肿瘤细胞，尤其是骨髓中肿瘤细胞的新型治疗策略具有可能性。
