Lin Ya-Ling, Ramanujum Rakesh, He Shiping
Department of Parasitology, China Medical University School of Medicine, Taichung 40402, Taiwan.
Asian Pac J Trop Biomed. 2011 Jan;1(1):23-8. doi: 10.1016/S2221-1691(11)60063-4.
To study whether the infection of Schistosomiasis japanicum (S. japanicum) is related to enhanced proliferation and migration of cancer cells, and the molecular mechanism pertains to cancer cell metastasis in human host.
The gene of S. japanicum glutathione transferase (sjGST) cloned from S. japanicum was expressed, purified and applied in a series of assays to explore the effect of sjGST on proliferation and migration of MDA-MB-435S, and the expression of MMP2 and MMP9. Immunofluorescence assay for the binding of sjGST to MDA-MB-435S was also carried out.
Results showed that sjGST enhanced proliferation and migration in human breast cancer cell MDA-MB-435S signifycantly at 50-200 nM, but did not enhance them in human lung cancer cell A549. Immunofluorescence assay for the binding of sjGST to MDA-MB-435S and A549 showed that GST was readily bound to the breast cancer cells, but showed almost no binding to human lung cancer cells. The assays for gelatinase activity showed that both MMP2 and MMP9 activities were increased significantly in the presence of sjGST (50-200 nM) in MDA-MB-435S, but they were not significant in A549.
Our current results show strongly that S. japanicum GST binds to MDA-MB-435S probably via its receptor, and enhances proliferation and migration of the cancer cells by up-regulatory expression of MMP2 and MMP9.
研究日本血吸虫感染是否与癌细胞增殖和迁移增强有关,以及其分子机制是否与人体宿主中的癌细胞转移有关。
表达、纯化从日本血吸虫克隆的日本血吸虫谷胱甘肽转移酶(sjGST)基因,并将其应用于一系列实验,以探讨sjGST对MDA-MB-435S细胞增殖、迁移以及MMP2和MMP9表达的影响。还进行了sjGST与MDA-MB-435S细胞结合的免疫荧光测定。
结果显示,50 - 200 nM的sjGST能显著增强人乳腺癌细胞MDA-MB-435S的增殖和迁移,但对人肺癌细胞A549无此作用。sjGST与MDA-MB-435S和A549细胞结合的免疫荧光测定表明,GST易于与乳腺癌细胞结合,但几乎不与人肺癌细胞结合。明胶酶活性测定显示,在MDA-MB-435S细胞中,50 - 200 nM的sjGST存在时,MMP2和MMP9的活性均显著增加,但在A549细胞中不显著。
我们目前的结果有力地表明,日本血吸虫GST可能通过其受体与MDA-MB-435S细胞结合,并通过上调MMP2和MMP9的表达来增强癌细胞的增殖和迁移。