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, scientists have revealed. 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.