Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer.
Adipocytes promote pancreatic cancer cell proliferation via glutamine transfer.
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DOI：
10.1016/j.bbrep.2016.06.004
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发表时间：
2016-09
影响因子：
2.7
通讯作者：
O'Rourke RW
中科院分区：
文献类型：
--
作者：
Meyer KA;Neeley CK;Baker NA;Washabaugh AR;Flesher CG;Nelson BS;Frankel TL;Lumeng CN;Lyssiotis CA;Wynn ML;Rhim AD;O'Rourke RW
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. 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.
