Liver cancer cells cause stromal cells to secrete proteins that contribute to tumor growth

Hepatocellular carcinoma (HCC), commonly seen in patients with cirrhosis of the liver caused by alcohol abuse or chronic viral hepatitis, is the most common form of liver cancer worldwide. Therefore, it is the third most common cause of cancer-related death and has a very poor prognosis. At present, surgery is the most effective treatment for HCC, but it is only successful in the 10% -20% of cases where cancer cells have not spread beyond the liver.

Given the lack of treatment options for HCC, a group of researchers led by Osaka University decided to focus on specific cells and processes occurring in the area around liver tumors in hopes of finding a new target for drug development.

The results of their study were published in a recent issue of Gastroenterology.

Hepatic stellate cells (HSCs) are normal liver cells that play a role in the formation of scar tissue in response to liver damage. High levels of activated HSCn have been reported in tumor microcirculation and are associated with poor prognosis in HCC patients. However, no one had studied the interaction between HSCn and liver cancer cells. “

Hayato Hikita, Study C.oAuthor

When the researchers cultured liver cancer cells in combination with HSCn, they saw a significant increase in the number of cancer cells, suggesting that the HSCs somehow stimulated cancer cell growth. Interestingly, however, inhibition of autophagy (a cellular process specifically designed to remove damaged or undesirable cellular components) in the HSCs inhibited the growth of cancer cells.

Using a mouse model of liver cancer and studying gene expression, the researchers made the interesting finding that the cancer cells actually stimulated autophagy in the HSCs, which led to the HSCs calling a protein called GDF15 , which stimulated tumor growth.

“When we examined liver samples from HCC patients with and without tumors, we found that the tumor suppressor samples had significantly higher levels of GDF15,” says lead author Tetsuo Takehara. “More importantly, however, when we examined the association between GDF15 expression and clinical outcome, we found that patients with higher levels of GDF15 had a worse prognosis than those with low levels of GDF15, which significantly highlighted the role of GDF15 in HCC progress. “

Building on the findings of this study, novel therapies targeting GDF15 expression with HSCn are an interesting new perspective for the treatment of HCC.