دورية أكاديمية
Pancreatic tumors exhibit myeloid-driven amino acid stress and upregulate arginine biosynthesis
| العنوان: | Pancreatic tumors exhibit myeloid-driven amino acid stress and upregulate arginine biosynthesis |
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| المؤلفون: | Juan J Apiz Saab, Lindsey N Dzierozynski, Patrick B Jonker, Roya AminiTabrizi, Hardik Shah, Rosa Elena Menjivar, Andrew J Scott, Zeribe C Nwosu, Zhou Zhu, Riona N Chen, Moses Oh, Colin Sheehan, Daniel R Wahl, Marina Pasca di Magliano, Costas A Lyssiotis, Kay F Macleod, Christopher R Weber, Alexander Muir |
| المصدر: | eLife, Vol 12 (2023) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | metabolism, tumor microenvironment, amino acid homeostasis, arginine, nutrient stress, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Nutrient stress in the tumor microenvironment requires cancer cells to adopt adaptive metabolic programs for survival and proliferation. Therefore, knowledge of microenvironmental nutrient levels and how cancer cells cope with such nutrition is critical to understand the metabolism underpinning cancer cell biology. Previously, we performed quantitative metabolomics of the interstitial fluid (the local perfusate) of murine pancreatic ductal adenocarcinoma (PDAC) tumors to comprehensively characterize nutrient availability in the microenvironment of these tumors. Here, we develop Tumor Interstitial Fluid Medium (TIFM), a cell culture medium that contains nutrient levels representative of the PDAC microenvironment, enabling us to study PDAC metabolism ex vivo under physiological nutrient conditions. We show that PDAC cells cultured in TIFM adopt a cellular state closer to that of PDAC cells present in tumors compared to standard culture models. Further, using the TIFM model, we found arginine biosynthesis is active in PDAC and allows PDAC cells to maintain levels of this amino acid despite microenvironmental arginine depletion. We also show that myeloid derived arginase activity is largely responsible for the low levels of arginine in PDAC tumors. Altogether, these data indicate that nutrient availability in tumors is an important determinant of cancer cell metabolism and behavior, and cell culture models that incorporate physiological nutrient availability have improved fidelity to in vivo systems and enable the discovery of novel cancer metabolic phenotypes. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/81289; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.81289 |
| URL الوصول: | https://doaj.org/article/c5f718ce140e4a6fa50f1ed1f45d288d |
| رقم الأكسشن: | edsdoj.5f718ce140e4a6fa50f1ed1f45d288d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.81289 |