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首页 » PLoS Pathog:寄生虫生长激素可激发肝癌发生

PLoS Pathog:寄生虫生长激素可激发肝癌发生

来源:生命经纬 2009-10-16 10:00

科学家发现人类的肝吸虫(Opisthorchis viverrini)对肝脏胆管的发育具有一定的作用,其能分泌颗粒体蛋白(一种生长激素)导致细胞肆意生长。这项研究结果发布在PLoS Pathogens上。

这项研究是由澳大利亚昆士兰州医学研究所,泰国孔敬大学,和乔治华盛顿大学的科学家共同完成的。据研究人员介绍,对于这项新发现--寄生虫的生长激素能够影响人类的细胞,他们是很兴奋。

肝吸虫分泌的蛋白能促进细胞生长,但是这种蛋白的身份还不是很清楚。同样我们知道寄生虫分泌颗粒体蛋白但是不知道其也会影响周围的人类细胞。

科研人员使用大肠杆菌表达肝吸虫的颗粒体蛋白。通过增加抗颗粒体蛋白抗体,他们发现细胞的芽殖增殖被终止了。因此确定颗粒体蛋白的作用是产生癌环境。

Loukas博士介绍说,这项研究为更好地理解寄生虫导致严重癌症发生的机制提供一个方向。(生物谷Bioon.com)

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PLoS Pathog 5(10): e1000611. doi:10.1371/journal.ppat.1000611

A Granulin-Like Growth Factor Secreted by the Carcinogenic Liver Fluke, Opisthorchis viverrini, Promotes Proliferation of Host Cells

Michael J. Smout1, Thewarach Laha2, Jason Mulvenna1, Banchob Sripa3, Sutas Suttiprapa3, Alun Jones4, Paul J. Brindley5, Alex Loukas1*

1 Division of Infectious Diseases, Queensland Institute of Medical Research, Queensland, Australia, and School of Population Health, The University of Queensland, Queensland, Australia, 2 Department of Parasitology, Khon Kaen University, Khon Kaen, Thailand, 3 Department of Pathology, Khon Kaen University, Khon Kaen, Thailand, 4 Institute for Molecular Biosciences, The University of Queensland, Queensland, Australia, 5 Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, D. C., United States of America

The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES) products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 was detected in situ on the surface of biliary epithelial cells of hamsters experimentally infected with O. viverrini. Recombinant Ov-GRN-1 was expressed in E. coli and refolded from inclusion bodies. Refolded protein stimulated proliferation of murine fibroblasts at nanomolar concentrations, and proliferation was inhibited by the MAPK kinase inhibitor, U0126. Antibodies raised to recombinant Ov-GRN-1 inhibited the ability of O. viverrini ES products to induce proliferation of murine fibroblasts and a human cholangiocarcinoma cell line in vitro, indicating that Ov-GRN-1 is the major growth factor present in O. viverrini ES products. This is the first report of a secreted growth factor from a parasitic worm that induces proliferation of host cells, and supports a role for this fluke protein in establishment of a tumorigenic environment that may ultimately manifest as cholangiocarcinoma.

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