Study shows that cancer impairs the ability of normal cells to consume glucose

Cancer needs energy to stimulate its uncontrollable growth. It consumes energy in the form of glucose. In fact, it consumes so much glucose that a method of imaging cancer simply looks for areas of extreme glucose consumption – where there is consumption, there is cancer. But how does cancer get this glucose? A study from the Cancer Center of the University of Colorado published today in the journal Cancer cell shows that leukemia reduces the ability of normal cells to consume glucose, leaving more glucose available to feed their own growth.

"Leukemia cells create a diabetes-like condition that reduces glucose to normal cells, so leukemia cells have more glucose, in fact they steal glucose from normal cells to stimulate tumor growth." says Craig Jordan, Ph.D., a research fellow at the University of Colorado Cancer Center, divisional head of the hematology division and professor of hematology at the University of Colorado at the University of Colorado.

Like diabetes, cancer control strategies depend on insulin. Healthy cells need insulin to use glucose. In case of diabetes, the pancreas by-product of insulin or tissues can not respond to insulin. The cells are therefore deprived of energy while the glucose accumulates in the blood. The present study shows that leukemia creates similar conditions for glucose accumulation in two ways.

First, tumor cells deceive fat cells by allowing them to overproduce a protein called IGFBP1. This protein makes healthy cells less sensitive to insulin, which means that when IGFBP1 is high, it takes more insulin to use glucose than when IGFBP1 is low. Unless the amount of insulin increases, a high IGFBP1 means that the glucose consumption of healthy cells decreases. (This protein can also be a link in the chain linking cancer and obesity: the more fat cells there are, the more IGFBP1 and more glucose is available for cancer.)

Of course, cancer has a second strategy that ensures that insulin production does not meet the need created by increasing IGFBP1 levels. In fact, cancers decrease the production of insulin. In large part, they do it in the intestine.

"During this systemic analysis, we realized that some of the factors that help regulate glucose are due to the intestine or bacteria in the intestine." We looked at the situation and found that the Microbiome composition in leukemic animals was different from that seen in leukemic animals: control mice, "says Jordan.

A major difference in the bowels of leukemic mice was the lack of specific type of bacteria called bacteroids. These bacteroids produce short chain fatty acids which in turn feed the health of the cells lining the intestine. Without bacteroids, intestinal health suffers. And the current study shows that, without bacteroids, bowel health suffers in a particularly beneficial way for cancer.

One way is the loss of hormones called incretins. When your blood sugar is high, for example after eating, your gut releases incretin, which lowers blood sugar and brings it back to normal. By working through the intestine, leukemia inactivates these incretins, allowing blood sugar to stay higher than it should. Leukemia also cancels the activity of serotonin. Serotonin is well known as a "feel good" chemical that helps regulate moods and is found in many antidepressants. But serotonin is also essential for the manufacture of insulin in the pancreas and, by attacking serotonin, leukemia reduces insulin production (and therefore, in the long run, l '. use of glucose).

The result of less secretion of insulin and less insulin sensitivity is that cancer compromises the use of insulin-like healthy cells on both sides: Healthy cells need to more insulin, just as there is less insulin available. Less use of insulin by healthy cells leaves more glucose for cancer.

"It's a classic thing against pests: take advantage of what the host does and flip it for your own purposes," Jordan says.

Interestingly, just as a parasite can eat the food of a host causing malnutrition, cancer-related energy theft can play a role in the fatigue and frequent weight loss in cancer patients.

"The fairly widespread observation is that cancer patients have a disease called cachexia, a disease that is wasting away, it's a weight loss." If cancers cause systemic changes resulting in the depletion of Normal energy reserves, that could be part of that story, "Jordan says.

However, Jordan and his colleagues, whose lead author Haobin Ye, PhD, not only showed how leukemia deregulates glucose consumption in healthy cells, but also showed how to "regulate" that consumption again.

"When we administered agents to recalibrate the glucose system, we found that we could restore glucose regulation and slow down the growth of leukemia cells," said Ye.

These "agents" were surprisingly little technological. One was serotonin. Another was tributyrin, a fatty acid found in butter and other foods. Serotonin supplementation replaced serotonin untreated with leukemia and tributyrin helped replace short-chain fatty acids absent due to bacteroid loss.

The group calls the association Ser-Tri therapy. And they show that it's more than a theory. Ser-Tri therapy was used to recover insulin levels and reduce IGFPB1. And leukemic mice treated with Ser-Tri therapy lived longer than those without. Twenty-two days after the introduction of leukemia in mice, all untreated mice were dead, while more than half of the mice treated with Ser-Tri were still alive.

The ongoing line of work shows that cancer can depend on the ability to compete with healthy cells for limited energy. Healthy tissues have strategies for regulating insulin, glucose and other factors controlling energy consumption. Cancer cells have strategies to reverse this regulation in order to make more energy available for their own use.

"We now have evidence that what we observed in our mouse models is also true for patients with leukemia." You say.

Understanding the mechanisms that cancer uses to unbalance the body's energy system helps doctors and researchers learn to progress in favor of healthy cells.

"This reinforces the idea that you can do things systematically to disadvantage leukemic cells and promote normal tissue," says Jordan. "This could be part of the limitation of tumor growth."