Press Release

Scientists at the Thomas N. Sato BioMEC-X Laboratories (ATR, Kyoto, Japan) have discovered a mechanism underlying how intestinal tumors affect the liver homeostasis, with the aid of a newly established zebrafish intestinal tumor model.

Our current knowledge of the mechanisms by which cancer adversely affects host organisms is limited. This is due at least in part to difficulties in examining the complex interactions between cancer and host in living animals. Now, in a new article published in Disease Models & Mechanisms, a team led by Dr. Shinpei Kawaoka reports on a novel experimental model suitable for addressing this issue, finding a molecular factor that mediates the effects of a tumor on the liver. They believe that this will be useful in advancing our understanding of tumor-host interaction, and in developing therapies that can ameliorate the adverse effects of cancer on a host.
In the newly established system, zebrafish larvae develop the intestinal tumor as early as 5 days post-fertilization, when they are small and transparent. The scientists are easily able to observe tumor tissues in live fish under a microscope, and to inspect interactions between tumor and host anywhere in the body. They found that the intestinal tumor causes a variety of adverse effects on the host, including liver inflammation, hepatomegaly (enlarged liver), growth defects, gene expression changes in normal organs, metabolic defects in the liver, and organismal death.
The model further enabled the researchers to investigate ongoing correlations between the tumor and the defects described above; in other words, to ask what will happen to the tumor’s effects on the host when the team specifically ‘cures’ gene expression changes in normal host organs. Investigations revealed that the intestinal tumor modifies cholesterol-bile metabolism in the liver possibly via down-regulation of a cholesterol-metabolizing gene cyp7a1, resulting in tumor-induced liver inflammation. “When we genetically normalize cholesterol-bile metabolism by over-expression of cyp7a1 in the liver of tumor-bearing fish, liver inflammation appears ameliorated, even though the intestinal tumor still exists”, explains Dr. Sora Enya, the lead author of the paper.
The number of cancer patients continues to increase, and despite advances in treatment there are still incurable cancers, in particular at the advanced stages. For this reason it is important to establish novel therapies that can protect patients from incurable cancers. “We would like to find a way to make organisms more ‘resistant’ to cancer’s adverse effects, and to improve patients’ quality of life in the future”, Kawaoka says.

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