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Abstract #2325

Glutamine transporter downregulation mediates metabolic reprogramming in pancreatic tumors

Raj Kumar Sharma1, Balaji Krishnamachary1, Ishwarya Sivakumar1, Yelena Mironchik1, Marie-France Penet1, Paul T Winnard Jr.1, Santosh K. Bharti1, and Zaver M. Bhujwalla1
1Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Pancreatic cancer cells are glutamine dependent for growth and proliferation. The glutamine transporter SLC1A5 is upregulated in pancreatic cancer and is being actively investigated as a pharmacological target. We genetically engineered human pancreatic cancer cells to express SLC1A5 shRNA to downregulate SLC1A5. 1H MRS was used to analyze metabolic differences in SLC1A5 downregulated Pa04C_SLC1A5 pancreatic cancer cells and tumors compared to empty vector cells and tumors. SLC1A5 downregulation resulted in a significantly lower glutamine/glutamate ratio in Pa04C_SLC1A5 cells. In Pa04C_SLC1A5 tumors we observed a significant reduction of several metabolites highlighting the metabolic reprogramming that occurred in tumors with SLC1A5 downregulation.

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