Parasite growth hormone pushes human cells to cancer

Scientists have found that the human liver fluke (Opisthorchis viverrini) contributes to the development of liver cancer by secreting granulin, a growth hormone that is known to cause uncontrolled cell growth.

Drs Michael Smout and Alex Loukas from the Queensland Institute of Medical Research (QIMR) say they are excited by the discovery which is the first research to show that a growth hormone from a parasite can affect human cells.

“It has been known that certain proteins secreted by O. viverrini cause cell growth, however 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.

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 of the bile ducts.

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

In northern Thailand, where the liver fluke is most common, more than 7 million people are infected at any given time. While less than 1% of people infected with other carcinogenic pathogens develop cancer (e.g. Helicobacter pylori and human papilloma virus), as many as 17% of people infected with O. viverrini could develop cholangiocarcinoma, one of the most fatal forms of liver cancer.

Previously, it was thought that cholangiocarcinoma 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). It is now thought that the granulin secreted by the parasite is a major contributing factor to developing bile duct cancer.

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, consequently proving granulin’s role in producing a cancerous environment.

This research was conducted in collaboration with The University of Queensland, Khon Kaen University in Thailand and George Washington University in the USA. Details are published October 9 in the open-access journal Public Library of Science Pathogens.