Parasite growth hormone pushes human cells to liver cancer

Scientists have found that the human liver fluke (Opisthorchis viverrini) contributes to the development of bile duct (liver) cancer by secreting granulin, a growth hormone that is known to cause uncontrolled growth of cells. Details are published October 9 in the open-access journal PLoS Pathogens.

Drs Michael Smout and Alex Loukas from the Queensland Institute of Medical Research, with collaborators at Khon Kaen University and George Washington University, say they are excited by the novel discovery which shows that a growth hormone from a parasite can affect human cells.

"It was known that O. viverrini secreted proteins cause cell growth, but the identity of the protein was unknown. We also knew that the parasite secreted granulin but we did not know that it could affect the human cells around it," said Dr Loukas.

Scientists used E. coli bacteria to express the O. viverrini granulin, which was shown to induce proliferation in mouse fibroblast cells and human bile duct cancer cells in the absence of the parasite. Proliferation of the cells was halted by adding anti-granulin antibody, thus proving granulin's role in producing a cancerous environment.

The International Agency for Research on Cancer classifies the human liver fluke as a Group I Carcinogen, meaning that O. viverrini is a proven cause of cancer. In northern Thailand, where the liver fluke is most common, more than 7 million people are infected at any given time.

Previously, it was thought that the cancer was caused by the physical damage brought about by the fluke feeding on cells lining the bile ducts, as well as a diet high in nitrosamines from fermented fish (a native dish of Thailand). Smout, Loukas and colleagues now suggest that the granulin secreted by the parasite is a major contributing factor to developing bile duct cancer.

"This discovery leads the way to a better understanding of how this parasite causes such a devastating form of cancer," said Dr. Loukas.

FINANCIAL DISCLOSURE: This research was supported by award number UO1AI065871 from the National Institute of Allergy and Infectious Diseases (the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID or the NIH), the Thailand-Tropical Diseases Research Program (T-2, grant number ID02-2-HEL-05-054) and the National Health and Medical Research Council, Australia (NHMRC). MJS is supported by a Dora Lush postgraduate scholarship from NHMRC. AL is supported by a senior research fellowship from NHMRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

COMPETING INTERESTS: The authors have declared that no competing interests exist.

PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.plos.org/10.1371/journal.ppat.1000611 (link will go live upon embargo lift)

CITATION: Smout MJ, Laha T, Mulvenna J, Sripa B, Suttiprapa S, et al. (2009) A Granulin-Like Growth Factor Secreted by the Carcinogenic Liver Fluke, Opisthorchis viverrini, Promotes Proliferation of Host Cells. PLoS Pathog 5(10): e1000611. doi:10.1371/journal.ppat.1000611

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