A new zebrafish study shows that a deadly form of skin cancer – melanoma – alters the metabolism of healthy tissue elsewhere in the body. Research from the University of Washington in St. Louis suggests that these other tissues could potentially be targeted to help treat cancer.
“Tumors depend 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 cases, this can even allow healthy tissues to grow. nourish the tumor, ”said Gary Patti, the Michael and Tana Powell professor of chemistry in arts and sciences at the University of Washington and professor of chemistry and medicine in the faculty of medicine.
Patti is the corresponding author of the study published May 13 in Cell metabolism.
Cancer consumes huge amounts of glucose, a key source of energy for the body’s cells. Glucose, or blood sugar, is derived from food and carried around the body through the bloodstream after eating. Tumors actively take up glucose for fuel to support their rapid growth.
This trait is so well known that doctors regularly use it as a diagnostic test for cancer, where patients are given a specific form of glucose that can be monitored with a PET scan. What is less clear is how a tumor addiction to glucose affects other tissues.
“Glucose levels are strictly regulated,” Patti said. “When the glucose levels get too low, it is dangerous. We wanted to know if a tumor with a high greed for glucose could influence the glucose levels in the blood.”
Even when healthy people go a long time without food, blood sugar levels remain relatively constant. This is because glucose can be produced by the liver when it cannot be obtained directly from food.
“Ultimately, the liver counteracts the impact of the tumor by synthesizing glucose,” Patti said. “It’s very similar to what happens during a fast.”
Working with the zebrafish, Patti and her co-authors, including other researchers from the School of Medicine, developed a new approach to study the impact of melanoma on different tissues in the body that uses a technology called metabolomics. .
Scientists fed zebrafish special versions of nutrients labeled with isotopic labels. These labels have allowed scientists to track where nutrients go and what molecules they are broken down into. They found that a molecule coughed up by the tumor was taken up by the liver to make glucose.
By applying metabolomics to each zebrafish, scientists observed that melanoma tissue in the body consumes about 15 times more glucose than 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 normally triggered when we go without eating.
But it was clear that otherwise healthy tissue was affected in many ways by the presence of melanoma.
Scientists examined tissue in the liver, intestine, fins, muscle, brain, blood, and eyes of zebrafish. They observed metabolic deregulation in most tissues – indicating that melanoma has an overall impact on the metabolism of the whole body.
“There is clear metabolic crosstalk between melanoma and other tissues,” Patti said. “The metabolic relationship between melanoma and the liver is in part characterized by a gene called BCAT1 in cancer cells. BCAT1 ranges from being primarily deactivated 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 true in people. “
Much of the previous cancer research has focused on the metabolism of the tumor itself.
“Our work shows that many interesting metabolic changes are also occurring beyond the tumor,” said Patti. “We have shown that, at least in some cases, these metabolic changes in non-malignant tissue occur to support the tumor. This is exciting because it means we may be able to target healthy tissue metabolism as a potential cancer treatment. . “