Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer
| Autor: | Costas A. Lyssiotis, Alexandra R. Washabaugh, Carey N. Lumeng, Barbara S. Nelson, Timothy L. Frankel, Michelle L. Wynn, Kevin A. Meyer, Christopher K. Neeley, Nicki A. Baker, Robert W. O'Rourke, Andrew D. Rhim, Carmen G. Flesher |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Stromal cell GSI glutamine synthetase inhibitor endocrine system diseases PDAC pancreatic ductal adenocarcinoma Glutamine GPNA l-glutamic acid-γ-p-nitroanilide-hydrochloride Biophysics Glutamine secretion GDH glutamate dehydrogenase Biology Biochemistry GS glutamine synthetase Pancreatic intraepithelial neoplasia 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine GLS glutaminase QRTPCR quantitative real-time polymerase chain reaction Adipocyte Internal medicine Pancreatic cancer medicine Glutaminase Cell growth PanIN pancreatic intraepithelial neoplasia medicine.disease 3T3L1 digestive system diseases 030104 developmental biology Endocrinology chemistry Cell culture 030220 oncology & carcinogenesis Gln glutamine Cancer research FCS fetal calf serum Research Article |
| Zdroj: | Biochemistry and Biophysics Reports |
| ISSN: | 2405-5808 |
| DOI: | 10.1016/j.bbrep.2016.06.004 |
| Popis: | Adipocytes promote progression of multiple cancers, but their role in pancreatic intraepithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC) is poorly defined. Nutrient transfer is a mechanism underlying stromal cell-cancer crosstalk. We studied the role of adipocytes in regulating in vitro PanIN and PDAC cell proliferation with a focus on glutamine metabolism. Murine 3T3L1 adipocytes were used to model adipocytes. Cell lines derived from PKCY mice were used to model PanIN and PDAC. Co-culture was used to study the effect of adipocytes on PanIN and PDAC cell proliferation in response to manipulation of glutamine metabolism. Glutamine secretion was measured with a bioanalyzer. Western blotting was used to study the effect of PanIN and PDAC cells on expression of glutamine-related enzymes in adipocytes. Adipocytes promote proliferation of PanIN and PDAC cells, an effect that was amplified in nutrient-poor conditions. Adipocytes secrete glutamine and rescue PanIN and PDAC cell proliferation in the absence of glutamine, an effect that was glutamine synthetase-dependent and involved PDAC cell-induced down-regulation of glutaminase expression in adipocytes. These findings suggest glutamine transfer as a potential mechanism underlying adipocyte-induced PanIN and PDAC cell proliferation. Highlights • Adipocytes promote pancreatic cancer cell proliferation in nutrient-poor conditions. • Adipocytes secrete glutamine. • Adipocytes rescue pancreatic cancer cell proliferation in the absence of glutamine. • Glutamine transfer may underlie adipocyte-induced pancreatic cancer cell proliferation. |
| Databáze: | OpenAIRE |
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