https://scholars.lib.ntu.edu.tw/handle/123456789/606863
標題: | Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells | 作者: | Tucci J Chen T Margulis K Orgel E Paszkiewicz R.L Cohen M.D Oberley M.J Wahhab R Jones A.E Divakaruni A.S CHENG-CHIH HSU Noll S.E Sheng X Zare R.N Mittelman S.D. |
關鍵字: | adipocytes;FFA;leukemia;lipid droplets;microenvironment;acetyl coenzyme A carboxylase;carboxylyase;citrinin;cytochrome c;daunorubicin;dexamethasone;etomoxir;fat droplet;fatty acid synthase;fenofibrate;gentamicin;glucose transporter 4;glycerol;interleukin 12;interleukin 16;interleukin 6;interleukin 7;ketamine;lactic acid;macrophage inflammatory protein 1alpha;monocyte chemotactic protein 1;monounsaturated fatty acid;oleic acid;palmitic acid;peroxisome proliferator activated receptor gamma;phospholipid;RANTES;sterol regulatory element binding protein 1c;tetrahydrolipstatin;triacylglycerol;unsaturated fatty acid;vincristine;3T3-L1 cell line;acute lymphoblastic leukemia;adipocyte;adipose tissue;adolescent;adult;animal cell;animal tissue;Article;bioenergy;bone marrow biopsy;breathing rate;cancer chemotherapy;cancer resistance;cardiac muscle cell;cell killing;cell metabolism;cell proliferation;cell survival;chemotherapy;child;clinical trial (topic);coculture;confocal microscopy;controlled study;cytokine release;cytotoxicity;EC50;endoplasmic reticulum stress;fatty acid oxidation;flow cytometry;gene expression;glucose transport;glycolysis;human;human cell;human tissue;IC50;immunoblotting;immunofluorescence;immunofluorescence assay;inflammation;lipid metabolism;lipidomics;lipogenesis;lipolysis;macromolecule;male;mass spectrometry;mitochondrial respiration;mouse;nonhuman;nuclear reprogramming;obesity;oxidative phosphorylation;pentose phosphate cycle;protein expression;protein phosphorylation;respirometry;teratoma;treadmill exercise;treatment failure;young adult | 公開日期: | 2021 | 卷: | 11 | 來源出版物: | Frontiers in Oncology | 摘要: | Background: There is increasing evidence that adipocytes play an active role in the cancer microenvironment. We have previously reported that adipocytes interact with acute lymphoblastic leukemia (ALL) cells, contributing to chemotherapy resistance and treatment failure. In the present study, we investigated whether part of this resistance is due to adipocyte provision of lipids to ALL cells. Methods: We cultured 3T3-L1 adipocytes, and tested whether ALL cells or ALL-released cytokines induced FFA release. We investigated whether ALL cells took up these FFA, and using fluorescent tagged BODIPY-FFA and lipidomics, evaluated which lipid moieties were being transferred from adipocytes to ALL. We evaluated the effects of adipocyte-derived lipids on ALL cell metabolism using a Seahorse XF analyzer and expression of enzymes important for lipid metabolism, and tested whether these lipids could protect ALL cells from chemotherapy. Finally, we evaluated a panel of lipid synthesis and metabolism inhibitors to determine which were affected by the presence of adipocytes. Results: Adipocytes release free fatty acids (FFA) when in the presence of ALL cells. These FFA are taken up by the ALL cells and incorporated into triglycerides and phospholipids. Some of these lipids are stored in lipid droplets, which can be utilized in states of fuel deprivation. Adipocytes preferentially release monounsaturated FFA, and this can be attenuated by inhibiting the desaturating enzyme steroyl-CoA decarboxylase-1 (SCD1). Adipocyte-derived FFA can relieve ALL cell endogenous lipogenesis and reverse the cytotoxicity of pharmacological acetyl-CoA carboxylase (ACC) inhibition. Further, adipocytes alter ALL cell metabolism, shifting them from glucose to FFA oxidation. Interestingly, the unsaturated fatty acid, oleic acid, protects ALL cells from modest concentrations of chemotherapy, such as those that might be present in the ALL microenvironment. In addition, targeting lipid synthesis and metabolism can potentially reverse adipocyte protection of ALL cells. Conclusion: These findings uncover a previously unidentified interaction between ALL cells and adipocytes, leading to transfer of FFA for use as a metabolic fuel and macromolecule building block. This interaction may contribute to ALL resistance to chemotherapy, and could potentially be targeted to improve ALL treatment outcome. ? Copyright ? 2021 Tucci, Chen, Margulis, Orgel, Paszkiewicz, Cohen, Oberley, Wahhab, Jones, Divakaruni, Hsu, Noll, Sheng, Zare and Mittelman. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85105447139&doi=10.3389%2ffonc.2021.665763&partnerID=40&md5=e9a6042c2c0dfd583a26e533c182a68d https://scholars.lib.ntu.edu.tw/handle/123456789/606863 |
ISSN: | 2234943X | DOI: | 10.3389/fonc.2021.665763 |
顯示於: | 化學系 |
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