no wayAbout 100 years ago, German physiologist Otto Warburg discovered that tumor cells more glucose Promotes proliferation compared to healthy cells.1 This phenomenon diagnostic imaging A cancer-detecting technique in which doctors inject radioactive glucose and track the consumption of tumor cells.2
Researchers later discovered another sugar, fruit sugarIt promotes tumor growth, but the mechanism is unclear.3 Fructose and glucose have the same chemical formula but different atomic arrangements. “Given the role glucose plays in cancer metabolism and how glucose is used as a primary fuel, we were very interested in how fructose might play a similar role,” he said. Gary PettyHe is a biochemist and systems biologist at Washington University in St. Louis.
Now, in a new study, Patti and her team have discovered that: Fructose indirectly promotes tumor growth.: The liver promotes the proliferation of tumor cells by breaking down fructose into nutrients that tumor cells absorb.4 Research published in natureWe highlight the complex metabolic cross-talk between cancer cells and healthy tissues, providing potential anticancer therapeutic targets.
as follows: small intestine and liver To metabolize most of the dietary fructose, the team examined the effects of this sugar on tumors outside the tissues.5 They exposed mice with breast, cervical, or skin cancer tumors to a solution of high-fructose corn syrup, a form of fructose commonly consumed by people. Tumors from mice exposed to fructose grew faster than tumors from mice fed a sugar-free diet.
To understand how fructose promotes tumor growth, researchers cultured different types of cancer cells in laboratory dishes. They grew these cells with fructose, which has heavy isotopes of carbon that are incorporated into metabolites. When the researchers tracked the labeled carbons to map the sugar’s fate, they found that the cells barely metabolized fructose.
These results were “absolutely surprising,” said Patti, who expected cancer cells to fuel themselves by absorbing and breaking down fructose. The team wondered whether the absence or low activity of fructose-metabolizing enzymes was responsible for the neglect of sugar breakdown. Of course, biochemical analyzes have shown that cultured cancer cells lack the enzymes ketohexokinase-c and aldolase-b needed to process fructose.
Based on these data, Patti hypothesized that tissues that express the enzyme, such as the liver, break down fructose into fuel for cancer cells. As the researchers grew healthy liver cells with labeled sugars, they were able to track their uptake into the cells.
Next, the team wanted to see whether liver cells break down fructose into molecules that cancer cells elsewhere in the body can utilize. The researchers cultured healthy liver cells and cervical cancer cells in dishes separated by a membrane. Compared to cancer cells grown without hepatocytes, cancer cells cultured with hepatocytes proliferated significantly faster in the presence of fructose. Treatment with ketohexokinase inhibitors reduces proliferation of co-cultured cells, indicating that fructose metabolism in liver cells supports the growth of cancer cells.
As a result of analyzing the metabolites secreted by liver cells and the metabolites absorbed by cancer cells, the researchers found that cancer cells absorb lipids secreted by liver cells, especially lysophosphatidylcholine (LPC).
Next, the researchers investigated whether dietary fructose increases LPC in vivo. When they compared circulating lipid profiles in the serum of mice fed sugar-free and fructose-rich diets, they observed elevated LPC levels in the latter group.
Exposing mice to labeled fructose and tracking LPC in their serum helped Patti and his team confirm that the increased serum LPC came from dietary fructose. Tracking the fate of labeled LPCs has helped researchers understand how tumor cells process LPCs. They found that phosphatidylcholine (PC), a key component of the cell membrane in tumor cells, contained labeled carbons, indicating that the tumor converted LPC to PC.
“I think [this study is] “It’s actually very well thought out and very interesting.” Kayvan KeshariA biochemist and bioengineer at Memorial Sloan Kettering Cancer Center, he was not involved in the study. “[These results] “This presents a very interesting mechanism for how tumors in vivo can use nutrients from the host,” he said.
But he didn’t think the results were particularly surprising because researchers are increasingly showing that other cells convert nutrients into molecules that cancer cells can use. The next step is to see if the same mechanism occurs in humans.
“We need further data and further experiments in humans for validation. [the results]”Patti agreed. But this study is an important first step because it shows that it is possible to limit tumor progression by targeting metabolism in healthy tissue, he added. “It opens up a lot of potential therapeutic possibilities.”
