摘要
γ干扰素(IFN-γ)可通过增加MHCⅠ类分子或其它机制增强多种肿瘤的转移能力,而将T细胞共刺激分子B7基因导入肿瘤细胞能增强机体免疫系统对肿瘤的攻击。本文以Lipofectamine转染法将小鼠B7-1(mB7-1)基因导入B16黑色素瘤低转移株,导入空载体(只含neo基因)的B16细胞作对照。亲本B16细胞和基因转导细胞(B16-B7-1和B16-neo)经100U/ml IFN-γ预处理36小时后进行实验性肺转移试验,同时流式细胞分析细胞表面MHCⅠ类和Ⅱ类分子的表达。结果发现,IFN-γ预处理明显增强B16和B16-neo细胞的肺转移能力,而经IFN-γ预处理的B16-B7-1细胞转移能力并不增强,其实验性肺转移结节数与未经处理的对照组无差别。流式细胞分析显示IFN-γ预处理使B16、B16-neo和B16-B7-1三种细胞的MHCⅠ类(H-2K^b和H-2D^b)分子均明显增高,但IFN-γ增加B16-B7-1细胞MHCⅡ类分子I-A^b表达程度显著高于其它两种细胞。结果表明,转导B7-1基因可降低IFN-γ诱导的B16细胞转移能力,MHCⅡ类分子表达增高可能在其中起一定作用。
Interferon y (IFN-γ) could enhance the metastatic potential of a variety of tumors via increasing expression of MHC class I molecules or other unidentified mechanisms. It has been demonstrated that transfection of T-cell costimulatory molecule B7 gene into tumor cells could increase tumor immunogenicity and render them susceptible to immune attack. In this study, we investigate whether transfection of B7-1 gene could antagonize IFN-γ-induced tumor metastasis. Lipofectamine-mediated transfection was used to introduce murine B7-1 (mB7-1) gene or neo gene into a low-metastatic variant of B16 melanoma cell line. The transfectants and parent B16 cells were treated with 100U/ml of IFN-γ for 36 h before being subjected to experimental metastasis assay. The expression of MHC class I and class II molecules on the cells was analysed by flow cytometry. Pre-treatment of parent B16 cells and mock gene-transfected B16 cells (B16-neo) with IFN-γ significantly increased their lung-metastizing capacity, while the same IFN-γ treatment of B16 cells transfected with mB7-1 gene (B16-B7-1) showed no increase in the number of lung metastatic nodules as compared with control cells. Almost equally elevated expression of MHC class I (H-2Kb and H-2Db) molecules was found on the surface of B16, B16-neo and B16-B7-1 cells. However, a much higher expression of class II (I-Ab) molecule on B16-B7-1 cells than that on B16 and B16-neo cells was observed. These results demonstrate that transfection of B7-1 gene into B16 melanoma could reduce its IFN-γ-induced metastasis and that the elevated MHC class II expression on B7-1-expressing cells might play a role in the B7-1 -associated reduction of metastasis.
出处
《中国肿瘤生物治疗杂志》
CAS
CSCD
1998年第2期85-89,共5页
Chinese Journal of Cancer Biotherapy
基金
国家自然科学基金(39470783)资助
