This team from the University of Colorado describes the process used by leukemia to hijack the metabolism and use sugar to find the energy it needs to grow. Work presented in the journal Cancer Cell that sheds light on the mechanisms of tumor growth and helps explain why many cancer patients develop cachexia , a sometimes fatal condition.
Because cancer needs energy to fuel its uncontrolled growth. A growth that consumes a lot of energy, in the form of glucose. The tumor consumes so much glucose that areas of extreme glucose consumption are often the very sites of the tumor. But how does cancer get this glucose? This is what this study from the Colorado Cancer Center explains to us, taking the example of leukemia: leukemia reduces the ability of normal cells to consume glucose in order to obtain more of it to nourish its own growth.
Leukemia cells lower glucose levels for normal cells, says Dr. Craig Jordan, researcher at the University of Colorado Cancer Center, head of the Department of Hematology and professor of hematology, and lead author of the study. So, like diabetes, cancer control strategies depend on insulin. Because cells need insulin to use glucose. In diabetes, glucose builds up in the blood. The study shows that leukemia induces similar glucose buildup in 2 ways:
- Tumor cells turn fat cells into a protein called IGFBP1. This protein makes healthy cells less sensitive to insulin, which means that when IGFB1 levels are high, more insulin is needed to utilize glucose than when IGFB1 levels are low. Thus, the glucose consumption of healthy cells decreases.
- A second strategy of tumor cells is to ensure that insulin production does not increase to meet the needs created by the increase in IGFBP1. Tumor cells decrease the production of insulin, and largely in the intestine.
The key role of the intestinal microbiome: the researchers show that some of the factors that regulate glucose are produced by the intestines or the bacteria of the intestinal microbiota. In particular, they observe that the composition of the microbiome in leukemic model animals is very different from control mice. In particular, the microbiota of leukemic mice is "severely" lacking in bacteroids, "good bacteria" that produce short-chain fatty acids that in turn fuel the health of the cells lining the gut. Without bacteroids, gut health suffers. The study thus shows that without bacteroids, gut health suffers in a way that specifically helps cancer to grow.
The loss of incretin hormones : When blood sugar is high, for example after eating, the intestine releases incretins which lower blood sugar and bring it back to normal. By impacting the gut, leukemia inactivates these incretins, allowing blood sugar to stay higher than it should.
Leukemia also insulates serotonin activity . Serotonin is well known as a feel-good chemical that helps regulate mood and is found in many antidepressants. But serotonin is also essential for the production of insulin in the pancreas. By attacking serotonin, leukemia further reduces insulin production.
Why cancer patients develop cachexia: we better understand this sometimes fatal consequence of cancers, where patients “let themselves waste away” and lose weight. In question therefore, these systemic changes resulting in the depletion of normal energy reserves.
But it is possible to "re-regulate" this energy consumption: by recalibrating glucose metabolism in mouse models of leukemia, thanks to pharmacological agents, scientists show that they can restore glucose regulation and slow down in the same time the growth of leukemic cells. Which agents are these? Surprisingly low-tech agents: One is serotonin, the other is tributyrin, a fatty acid found in butter and other foods. Serotonin supplementation replaced untreated serotonin in leukemia, and tributyrin helped replace short-chain fatty acids missing due to loss of bacteroids.
"Ser-Tri" (for serotonin-tributyrin), a new therapy? It is indeed more than a theory. Ser-Tri therapy recovered insulin levels and reduced IGFPB1. And leukemic mice treated with Ser-Tri therapy lived longer than their control counterparts.
Thus, the growth of cancer greatly depends on its ability to steal energy from healthy cells. Preventing this energy system imbalance helps block cancer growth and protects healthy tissue.
