کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5527204 1401570 2017 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Tumor stroma interaction is mediated by monocarboxylate metabolism
ترجمه فارسی عنوان
تعامل استرومائی تومور بوسیله متابولیسم مونوکربوکیلات متاثر می شود
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
چکیده انگلیسی

Human breast tumors contain significant amounts of stromal cells. There exists strong evidence that these stromal cells support cancer development and progression by altering various pathways (e.g. downregulation of tumor suppressor genes or autocrine signaling loops). Here, we suggest that stromal carcinoma-associated fibroblasts (CAFs), shown to be generated from bone marrow-derived mesenchymal stem cells, may (i) recycle tumor-derived lactate for their own energetic requirements, thereby sparing glucose for neighboring glycolytic tumor cells, and (ii) subsequently secrete surplus energetically and biosynthetically valuable metabolites of lactate oxidation, such as pyruvate, to support tumor growth. Lactate, taken up by stromal CAFs, is converted to pyruvate, which is then utilized by CAFs for energy needs as well as excreted and shared with tumor cells. We have interrogated lactate oxidation in CAFs to determine what metabolites may be secreted, and how they may affect the metabolism and growth of MDA-MB-231 breast cancer cells. We found that CAFs secrete pyruvate as a metabolite of lactate oxidation. Further, we show that pyruvate is converted to lactate to promote glycolysis in MDA-MB-231 cells and helps to control elevated ROS levels in these tumor cells. Finally, we found that inhibiting or interfering with ROS management, using the naturally occurring flavonoid phloretin (found in apple tree leaves), adds to the cytotoxicity of the conventional chemotherapeutic agent doxorubicin. Our work demonstrates that a lactate-pyruvate, reciprocally-supportive metabolic relationship may be operative within the tumor microenvironment (TME) to support tumor growth, and may be a useful drug target.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 352, Issue 1, 1 March 2017, Pages 20-33
نویسندگان
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