A new study with zebrafish shows that melanoma alters the metabolism of healthy tissues elsewhere in the body. The research from Washington University in St. Louis suggests that these other tissues could potentially be targeted to help treat cancer.
"Tumors rely on a constant supply of nutrients to grow. Instead of competing with tumors for nutrients, other tissues can reprogram their metabolism to be complementary. In some instances, this may even allow healthy tissues to feed the tumor," said Gary Patti, corresponding author of the study published today in Cell Metabolism.
For the study, the team fed the zebrafish special versions of nutrients tagged with isotope labels. These labels allowed the scientists to track where nutrients go and into what molecules they get broken down. They found that a molecule being spit out by the tumor was being taken up by the liver to make glucose.
By applying metabolomics to individual zebrafish, the scientists observed that melanoma tissues in the body consume about 15 times more glucose than the other tissues they measured. Despite this burden, the zebrafish were able to maintain circulating glucose levels, apparently by making glucose in the liver through a process that is ordinarily triggered when we go without eating.
But it was clear that otherwise healthy tissues were affected in many ways by the presence of melanoma. The scientists examined tissues in the liver, intestine, fin, muscle, brain, blood, and eye of the zebrafish. They observed metabolic dysregulation across most of the tissues—indicating that melanoma broadly impacts whole-body metabolism.
"There is clear metabolic crosstalk between melanoma and other tissues," Patti said. "The metabolic relationship between melanoma and liver is partly characterized by a gene called BCAT1 in the cancer cells. BCAT1 goes from essentially being turned off in healthy skin cells to being highly expressed in zebrafish melanoma. By looking at melanoma from human patients, we were able to confirm that the same pattern holds in people."