Lab talk: The healing powers of worm spit


We ask scientists to tell us about their discoveries and explain why they matter.


Michael Smout says the consumption of uncooked fish may explain the prevalence of liver cancer in Asia. – OK-White Lane/International FameLab

Southeast Asia has a strikingly high prevalence of a type of liver cancer called cholangiocarcinoma (CCA), which kills 26,000 people in the region each year. It’s linked to eating raw fish, a staple part of the diet in Laos and northeast Thailand.

Uncooked fish can harbour the liver worm Opisthorchis viverrini and the evidence incriminating the parasite is strong: one in six people infected with it develop CCA. By comparison fewer than one in 100 women infected with the human papillomavirus will develop cancer of the cervix.

The cancer-causing culprit in the worm appears to be one of the molecules secreted in their “spit”. Worm spit causes cells to multiply more quickly than normal, a well-known stage in the initiation of many cancers.

While analysing the molecules that make up worm spit, we discovered one similar to a natural human “growth factor” molecule called granulin. It plays a role in embryonic development, wound healing and many aggressive human cancers.

We produced worm granulin in the laboratory and confirmed it triggers excessive cell growth. We also showed antibodies against worm granulin block that ability, confirming that worm granulin is a major growth inducing protein.

Why would the worm release a compound that causes human cells to grow prolifically? We suspect the parasite may be “farming” the cells for nutrition. Alternatively, perhaps granulin tweaks the human immune system so that it fails to notice the parasite.

A section of a liver worm in a human bile duct. The worms cause cancer and evidence is strong that the culprit is a chemical in its spit. – Professor Banchob Sripa

Either way, the worm’s trick may also be its Achilles heel. Our work shows that when we block granulin production, the parasite’s health declines dramatically. Knowing this, we are investigating how to develop an “anti-granulin” vaccine to try and help the nine million infected people in Southeast Asia. But our work may not only be beneficial for cancer prevention. Granulin has potent wound healing properties and we are exploring future applications to treat wounds that don’t heal – a common problem in the elderly and diabetics.

Watch this space – maybe one day you’ll be seeing granulin-coated Band-Aids.

Paper: The tumorigenic liver fluke Opisthorchis viverrini - multiple pathways to cancer. Trends in Parasitology, 2012, vol 28, p395-407.
Paper: Infection with the carcinogenic human liver fluke, Opisthorchis viverrini. Molecular BioSystems, 2011, vol 7, p1367-1375.

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