科學(xué)家發(fā)現(xiàn)人類的肝吸蟲(Opisthorchis viverrini)對肝臟膽管的發(fā)育具有一定的作用,,其能分泌顆粒體蛋白(一種生長激素)導(dǎo)致細胞肆意生長,。這項研究結(jié)果發(fā)布在PLoS Pathogens上,。
這項研究是由澳大利亞昆士蘭州醫(yī)學(xué)研究所,,泰國孔敬大學(xué),和喬治華盛頓大學(xué)的科學(xué)家共同完成的,。據(jù)研究人員介紹,,對于這項新發(fā)現(xiàn)--寄生蟲的生長激素能夠影響人類的細胞,他們是很興奮,。
肝吸蟲分泌的蛋白能促進細胞生長,,但是這種蛋白的身份還不是很清楚。同樣我們知道寄生蟲分泌顆粒體蛋白但是不知道其也會影響周圍的人類細胞,。
科研人員使用大腸桿菌表達肝吸蟲的顆粒體蛋白,。通過增加抗顆粒體蛋白抗體,他們發(fā)現(xiàn)細胞的芽殖增殖被終止了,。因此確定顆粒體蛋白的作用是產(chǎn)生癌環(huán)境,。
Loukas博士介紹說,這項研究為更好地理解寄生蟲導(dǎo)致嚴重癌癥發(fā)生的機制提供一個方向,。(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.