“We see in liver cells not only an abnormal accumulation of fat but also a shift away from the normal processing of lipids, so that the lipids that are being produced are more advantageous to the cancer,” said co-senior author Dr. The scientists suspect that the fatty liver condition benefits cancers in part by turning the liver into a lipid-based source of energy to fuel cancer growth. Jianlong Li, a scientific collaborator in the Lyden laboratory, is also a co-first author of the study. Gang Wang, a postdoctoral associate in the Lyden laboratory. “One of our more striking observations was that this EVP-induced fatty liver condition did not co-occur with liver metastases, suggesting that causing fatty liver and preparing the liver for metastasis are distinct strategies that cancers use to manipulate liver function,” said co-first author Dr. When taken up by liver-resident immune cells called Kupffer cells, the fatty acid cargo triggers the production TNF-α, which consequently drives fatty liver formation.Īlthough the researchers principally used animal models of cancers in the study, they observed similar changes in the livers of newly diagnosed pancreatic cancer patients who later developed non-liver metastases. The researchers traced this liver reprogramming to EVPs that are released by the distant tumors and carry fatty acids, especially palmitic acid. The observed reduction in cytochrome P450 levels could explain why cancer patients often become less tolerant of chemotherapy and other drugs as their illness progresses. The team also observed that reprogrammed livers have high levels of inflammation, marked by elevated level of tumor necrosis factor-α (TNF-α), and low levels of drug-metabolizing enzymes called cytochrome P450, which break down potentially toxic molecules, including many drug molecules. The study’s key finding is that these tumors induce accumulation of fat molecules in liver cells, consequently reprogramming the liver in a way that resembles the obesity- and alcohol-related condition known as fatty liver disease. In the new study, the researchers uncovered a different set of liver changes caused by distant cancer cells which they observed in animal models of bone, skin and breast cancer that metastasize to other organs but not to the liver. In their work published in 2015, for example, the team discovered that pancreatic cancers secrete molecules encapsulated in extracellular vesicles, that travel through the bloodstream, are taken up by the liver, and prepare the organ to support the outgrowth of new, metastatic tumors. These effects reflect specific strategies cancers use to secure their survival and speed their progression. Lyden, who is also a member of the Gale and Ira Drukier Institute for Children’s Health and the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, and his research group have been studying the systemic effects of cancers. Niarchos Professor in Pediatric Cardiology and a professor of pediatrics and of cell and developmental biology at Weill Cornell Medicine.įor the past two decades, Dr. “Our findings show that tumors can lead to significant systemic complications including liver disease, but also suggest that these complications can be addressed with future treatments,” said study co-senior author Dr.
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