کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8456889 | 1548783 | 2017 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The Stromal Microenvironment Modulates Mitochondrial Oxidative Phosphorylation in Chronic Lymphocytic Leukemia Cells
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کلمات کلیدی
qPCRNTPBCROXPHOSmTORMRCECAROCRCLLMitochondrial DNA - DNA میتوکندریاROS - ROSMitochondrial mass - توده میتوکندریmtDNA - دیانای میتوکندریاییribonucleoside triphosphate - ریبونوکلئوزید تری فسفاتelectron transport chain - زنجیره انتقال الکترونextracellular flux - شار خارج سلولیMitochondrial oxidative phosphorylation - فسفوریلاسیون اکسیداتیو MitohondrialChronic lymphocytic leukemia - لوسمی مزمن لنفوئیدیMOMP - ماموریتOxygen consumption rate - میزان مصرف اکسیژنextracellular acidification rate - نرخ اسیدی شدن خارج سلولیMechanistic target of rapamycin - هدف مکانیکی رپامایسینETc - و غیرهquantitative polymerase chain reaction - واکنش زنجیره ای پلیمراز کمیReactive oxygen species - گونههای فعال اکسیژنB-cell receptor - گیرنده سلول B
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Peripheral blood chronic lymphocytic leukemia (CLL) cells are replicationally quiescent mature B-cells. In short-term cultures, supporting stromal cells provide a survival advantage to CLL cells by inducing transcription and translation without promoting proliferation. We hypothesized that the stromal microenvironment augments malignant B cells' metabolism to enable the cells to cope with their energy demands for transcription and translation. We used extracellular flux analysis to assess the two major energy-generating pathways, mitochondrial oxidative phosphorylation (OxPhos) and glycolysis, in primary CLL cells in the presence of three different stromal cell lines. OxPhos, measured as the basal oxygen consumption rate (OCR) and maximum respiration capacity, was significantly higher in 28 patients' CLL cells cocultured with bone marrow-derived NK.Tert stromal cells than in CLL cells cultured alone (P = .004 and <.0001, respectively). Similar OCR induction was observed in CLL cells cocultured with M2-10B4 and HS-5 stromal lines. In contrast, heterogeneous changes in the extracellular acidification rate (a measure of glycolysis) were observed in CLL cells cocultured with stromal cells. Ingenuity Pathway Analysis of CLL cells' metabolomics profile indicated stroma-mediated stimulation of nucleotide synthesis. Quantitation of ribonucleotide pools showed a significant two-fold increase in CLL cells cocultured with stromal cells, indicating that the stroma may induce CLL cellular bioenergy and the RNA building blocks necessary for the transcriptional requirement of a prosurvival phenotype. The stroma did not impact the proliferation index (Ki-67 staining) of CLL cells. Collectively, these data suggest that short-term interaction (â¤24 hours) with stroma increases OxPhos and bioenergy in replicationally quiescent CLL cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 19, Issue 10, October 2017, Pages 762-771
Journal: Neoplasia - Volume 19, Issue 10, October 2017, Pages 762-771
نویسندگان
Hima V. Vangapandu, Mary L. Ayres, Christopher A. Bristow, William G. Wierda, Michael J. Keating, Kumudha Balakrishnan, Christine M. Stellrecht, Varsha Gandhi,