Zhou Huimin, Jia Li, Wang Shujing, Wang Hongmei, Chu Haiying, Hu Yichuan, Cao Jun, Zhang Jianing
Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, Dalian 116027, China.
Biochem Biophys Res Commun. 2006 Jun 23;345(1):486-94. doi: 10.1016/j.bbrc.2006.03.246. Epub 2006 May 2.
Caveolin-1 is the major component protein of caveolae and associated with a lot of cellular events such as endocytosis, cholesterol homeostasis, signal transduction, and tumorigenesis. The majority of results suggest that caveolin-1 might not only act as a tumor suppressor gene but also a promoting metastasis gene. In this study, the divergent expression and roles of caveolin-1 were investigated in mouse hepatocarcinoma cell lines Hca-F, Hca-P, and Hepa1-6, which have high, low, and no metastatic potential in the lymph nodes, as compared with normal mouse liver cell line IAR-20. The results showed that expression of caveolin-1 mRNA and protein along with the amount of caveolae number in Hca-F cells was higher than that in Hca-P cells, but was not detectable in Hepa1-6 cells. When caveolin-1 expression in Hca-F cells was down-regulated by RNAi approach, Hca-F cells proliferation rate in vitro declined and the expression of lymphangiogenic factor VEGFA in Hca-F decreased as well. Furthermore, in vivo implantation assay indicated that reduction of caveolin-1 expression in Hca-F prevented the lymphatic metastasis tumor burden of Hca-F cells in 615 mice. These results suggest that caveolin-1 facilities the lymphatic metastasis ability of mouse hepatocarcinoma cells via regulation tumor cell growth and VEGFA expression.
小窝蛋白-1是小窝的主要组成蛋白,与许多细胞事件相关,如内吞作用、胆固醇稳态、信号转导和肿瘤发生。大多数结果表明,小窝蛋白-1不仅可能作为一种肿瘤抑制基因,还可能是一种促进转移的基因。在本研究中,与正常小鼠肝细胞系IAR-20相比,研究了小窝蛋白-1在具有高、低和无淋巴结转移潜能的小鼠肝癌细胞系Hca-F、Hca-P和Hepa1-6中的差异表达及作用。结果显示,Hca-F细胞中小窝蛋白-1 mRNA和蛋白的表达以及小窝数量均高于Hca-P细胞,但在Hepa1-6细胞中未检测到。当通过RNAi方法下调Hca-F细胞中小窝蛋白-1的表达时,Hca-F细胞的体外增殖率下降,Hca-F中淋巴管生成因子VEGFA的表达也降低。此外,体内植入试验表明,Hca-F中小窝蛋白-1表达的降低可减轻615小鼠中Hca-F细胞的淋巴转移肿瘤负荷。这些结果表明,小窝蛋白-1通过调节肿瘤细胞生长和VEGFA表达促进小鼠肝癌细胞的淋巴转移能力。