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

Hepatocellular carcinoma (HCC), which is frequently found in patients with cirrhosis caused by alcohol abuse or chronic viral hepatitis, is the most common form of liver cancer in the world. Thus, it is the third most common cause of cancer-related death and has a notorious poor prognosis. Currently, surgery is the most effective treatment for HCC, but it is only successful in 10% to 20% of cases where the cancer cells have not spread beyond the liver.

Due to the lack of treatment options for HCC, a group of researchers leading Osaka University will focus on specific cells and processes that occur around liver tumors in the hope of finding new targets for drug development. I decided.

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

Hepatocytes (HSCs) are normal hepatocytes and are involved in the formation of scar tissue in response to liver damage. High levels of activated HSC have been reported in the tumor microenvironment and are associated with a poor prognosis in patients with HCC. But no one has investigated the interaction of HSCs with cancer cells in the liver. “

Hayato Hiketa, Study CoAuthor

When researchers cultured liver cancer cells with HSCs, they observed a significant increase in the number of cancer cells, suggesting that HSCs somehow promoted cancer cell growth. Interestingly, inhibition of autophagy (a cellular process designed primarily to remove damaged or unwanted cellular components) in HSC prevented the growth of cancer cells.

Using a mouse model of liver cancer and analysis of gene expression, researchers found that cancer cells actually induce autophagy in HSCs, which causes HSCs to secrete a protein called GDF15, which promotes tumor growth. I made an amazing discovery to do.

“Examination of liver samples from HCC patients with and without tumors showed that tumor tissue samples had much higher GDF15 levels,” said senior author Tetsuo Takehara. “But most importantly, when we examined the association between GDF15 expression and clinical outcomes, we found that patients with high GDF15 expression had a worse prognosis than patients with low GDF15 expression, and in HCC. The role of GDF15 has been clarified. Progress. “

Based on the findings of this study, new therapies targeting GDF15 expression by HSC are exciting new perspectives for the treatment of HCC.

Source:

Journal reference:

Myojin, Y. , et al.. (2020) Hepatocellular carcinoma Hepatocellular carcinoma promotes tumor growth through the production of growth differentiation factor 15. Gastroenterology. doi.org/10.1053/j.gastro.2020.12.015.

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

Source link Liver cancer cells cause stromal cells to secrete proteins that promote tumor growth

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