The Expression and Activity of MMPs Are Increased in Residual Tumor Tissues after the Termination of Immunotherapy

被引:1
作者
Xiong, Ting [1 ]
Peng, Huimin [1 ]
Chen, Guoxi [1 ]
Yuan, Ye [1 ]
机构
[1] Huazhong Univ Sci & Technol, Dept Biochem & Mol Biol, Tongji Med Coll, Wuhan 430030, Peoples R China
基金
中国国家自然科学基金;
关键词
immunotherapy; tumor metastasis; interferon gamma; matrix metalloproteinases;
D O I
10.1007/s11596-008-0401-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To investigate the invasive ability of the residual tumor cells after immunotherapy and explore the feasible approach suppressing the invasion, mice were inoculated with B16 cells, and then treated by gene therapy with p4-1BBL/psPD-1 or IFN-gamma. The production and activities of MMP-9 and MMP-2 in residual tumor tissues were analyzed with gelatin zymography 1 day and 7 days after the termination of the immunotherapy. The production of MMP-9 and MMP-2 by B16 cells treated with IFN-gamma was also analyzed. IFN-gamma-treated B16 cells were inoculated to mice via subcutaneous injection. The invasion of tumor to muscular tissue was analyzed. Gene therapy with CH50 was used to suppress the invasive growth of tumor. The results showed that the expression and the activities of MMP-9 and MMP-2 were significantly increased 7 days after the end of immunotherapy. The response of tumor cells to ECM molecules was intensified after the removal of IFN-gamma, resulting in significant increase of both the production and activities of MMP-9 and MMP-2, and the increased invasion of tumor. Gene therapy with CH50 effectively suppressed the invasive growth of tumor. It is concluded that the termination of immunotherapy may result in a higher metastatic potential of residual tumor cells. Suppressing tumor invasion by suitable treatment will improve the efficacy of immunotherapy.
引用
收藏
页码:375 / 378
页数:4
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