Two hormone factors, cortisol and serotonin, play critical roles in the development of male-biased liver cancers, biologists report.
Liver cancer occurs more frequently in males than females. This suggests that sex hormones might be involved in the development of liver cancers. However, clinical trials targeting sex hormones did not produce sufficiently convincing results, suggesting that other factors might also be involved.
Zebrafish liver tumors share remarkable similarity with human liver tumors in terms of disease markers, molecular pathways, and other features.
Using a liver tumor model in krasv12 transgenic zebrafish, a research group at the National University of Singapore found that some other factors that are not sex hormones play critical roles in the sex disparity of liver cancers.
In one study, they found that a glucocorticoid hormone, cortisol, is produced more than usual in male zebrafish with liver cancers. This hormone could trigger two different types of white blood cells, neutrophils and macrophages, which in turn enhance the development of liver cancer.
In another study, they found that serotonin, a neurotransmitter, is also produced more than usual in male oncogenic livers. This again can cause the growth of liver cancer through the activation of a major cell type involved in liver diseases (hepatic stellate cells).
These findings have also been validated in human liver disease samples.
“The current studies highlight the importance of some non-sex hormones in the development of male-biased liver cancer and this may prompt us to have alternative and supplementary therapeutic strategies in fighting it,” says team leader and professor Gong Zhiyuan.
Apart from strengthening confidence in using zebrafish to study human liver cancers, the work could lead to new potential therapeutic targets for the treatment of liver cancers. This can also be extended to other types of cancer that show sex disparity, particularly those of the digestive tract.
The researchers report their work in Cancer Research and Cellular and Molecular Gastroenterology and Hepatology.
Source: National University of Singapore