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Researchers identify a mechanism that fuels cancer cells’ growth

UCLA Research Alert

Post Date:November 14, 2018 11:00 AM
UCLA cancer researchers Drs. Claudio Scafoglio (left) and David Shackelford

Scientists at the UCLA Jonsson Comprehensive Cancer Center have identified sodium glucose transporter 2, or SGLT2, as a mechanism that lung cancer cells can utilize to obtain glucose, which is key to their survival and promotes tumor growth. The finding provides evidence that SGLT2 may be a novel biomarker that scientists can use to help diagnose precancerous lung lesions and early-stage lung cancers.

BACKGROUND
Cancer cells require large amounts of glucose to survive and grow. Past research has established that passive glucose transporters, or GLUTs, are the primary means the body uses to deliver glucose to tumors. However, more recent studies have found some cancers, such as prostate and pancreatic, also rely on SGLT2 to utilize glucose, which spurred the UCLA scientists to study the role of SGLT2 in relation to lung cancer.

Glucose transport evolves during lung adenocarcinoma development. Early-stage cancers use SGLT2 but not GLUTs to take up glucose, and can be imaged with the SGLT-specific tracer Me4FDG but not GLUT-specific tracer FDG. Late-stage cancers can take up glucose through both transporters, and they are positive for both Me4FDG and FDG

Finding ways to diagnose lung cancer earlier when it is easier to treat is imperative because it is currently the leading cause of cancer-related deaths in both men and women worldwide.

METHOD
The researchers used positron emission tomography, or PET scans, to capture SGLT activity in lung cancer cells. They were able to use SGLT2 activity to guide how they used SGLT2 inhibitors to treat mice with genetic models of lung cancer and other mice that had been implanted with human lung tumors.

The researchers found unusually high levels of SGLT2 in human specimens of lung cancer, showing that these tumors predominantly utilize SGLT2, but not GLUTs, to transport glucose in the early stages of tumor growth and even in pre-malignant lesions that precede the development of lung cancer.

IMPACT
The study suggests that lung cancer can be detected earlier, when it is much easier to treat. By using SGLT2 as a biomarker, lung cancer could not only be found earlier than it often is today, but it could potentially be discovered even before lesions become cancerous. The researchers also provided evidence that a common FDA-approved inhibitor drug (which is currently used to treat diabetes) could help block SGLT2 activity in cancer cells. The inhibitor could be used to block glucose uptake and help reduce tumor growth.

AUTHORS
The study’s lead author is Claudio Scafoglio, assistant professor of pulmonary and critical care medicine at UCLA and a member of the Jonsson Cancer Center. The senior author is David Shackelford, associate professor of pulmonary and critical care medicine at UCLA and a member of the Jonsson Cancer Center. Other authors, all of UCLA, are Steven Dubinett, Brendon Villegas, Gihad Abdelhady, Sean Bailey, Jie Liu, Aditya Shirali, Dean Wallace, Clara Magyar, Tristan Grogan, David Elashoff, Tonya Walser, Jane Yanagawa, Denise Aberle and Jorge Barrio.

JOURNAL
The research is published online in Science Translational Medicine.

FUNDING
The study was supported by the National Center for Advancing Translational Sciences, a UCLA Clinical and Translational Science Institute KL2 Translational Science Award, the American Cancer Society, the Tobacco Related Disease Research Program, the Stop Cancer Foundation, a Saul Brandman Program grant, a Department of Defense Lung Cancer Research Program grant, merit review research funds from the Department of Veterans Affairs, an NIH/NHLBI training grant, and a Thoracic Surgery Foundation Research Award.

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