Scientists have found that Some Types of Cancers have more of a Sweet Tooth than others

Researchers at the University of Texas at Dallas have found that two types of non-small cell lung cancer metabolize glucose — a type of sugar — differently. A glucose transporter called GLUT1, shown in green, is much more prevalent in lung squamous cell carcinoma cells (right) in comparison to lung adenocarcinoma cells (left). The findings, published in the online journal Nature Communications, may aid the development of new lung cancer therapies targeted at inhibiting GLUT1. Credit: University of Texas at Dallas

In a new study, The University of Texas at Dallas scientists have found that some types of cancers have more of a sweet tooth than others. “It has been suspected that many cancer cells are heavily dependent on sugar as their energy supply, but it turns out that one specific type – squamous cell carcinoma – is remarkably more dependent,” said Dr. Jung-whan “Jay” Kim, assistant professor of biological sciences.

Kim and his collaborators initially set out to investigate differences in metabolism between 2 major subtypes of non-small cell lung cancer – adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). About 1/4 of all lung cancers are SqCC, which has been difficult to treat with targeted therapies. The team, which included a Dallas high school student who interned in Kim’s lab, first tapped into a large government database called The Cancer Genome Atlas, which maps information about 33 types of cancer gathered from more than 11,000 patients.

Based on that data, they found that a protein, GLUT1, responsible for transporting glucose into cells was present in much higher levels in lung SqCC than in lung ADC. Glucose transporter 1 is also necessary for normal cell function, such as building cell membranes. Kim said. “These findings lend credence to the idea that cancer is not just one disease, but many diseases that have very different characteristics.”

With elevated GLUT1 implicated in SqCC’s appetite for sugar, the researchers looked for additional evidence by examining human lung tissue and isolated lung cancer cells, as well as animal models of the disease. “We looked at this from several different experimental angles, and consistently, GLUT1 was highly active in the squamous subtype of cancer. Adenocarcinoma is much less dependent on sugar,” Kim said. “Our study is the first to show systematically that the metabolism of these two subtypes are indeed distinct and unique.”

The researchers also investigated the effect of a GLUT1 inhibitor in isolated lung cancer cells and mice with both types of non-small cell lung cancer. “When we gave GLUT1 inhibitors to mice with lung cancer, the squamous cancer diminished, but not the adenocarcinoma,” Kim said. “There was not a complete eradication, but tumor growth slowed. “GLUT1 could be a potential target for new lines of drug therapy, especially for the squamous subtype of cancer.”

In addition to squamous cell lung cancer, the team found that GLUT1 levels were much higher in 4 other types of squamous cell cancer: head and neck, esophageal and cervical. An upcoming study will examine the effect of a sugar-restricted diet on the progression of lung cancer in an animal model of the disease. The U.S. Department of Agriculture estimates that in 2015, on average, each American consumed more than 75 pounds of refined sugar, high fructose corn syrup and other sweeteners combined.

“As a culture, we are very addicted to sugar,” Kim said. “Excessive sugar consumption is not only a problem that can lead to complications like diabetes, but also, based on our studies and others, the evidence is mounting that some cancers are also highly dependent on sugar. We’d like to know from a scientific standpoint whether we might be able to affect cancer progression with dietary changes.”
http://www.utdallas.edu/news/2017/5/30-32567_Scientists-Study-Sweetens-Connection-Between-Cance_story-wide.html?WT.mc_id=NewsHomePageCenterColumn