Modeling the bidirectional glutamine/ammonium conversion between cancer cells and cancer-associated fibroblasts.
Modeling the bidirectional glutamine/ammonium conversion between cancer cells and cancer-associated fibroblasts.
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作者：
Hinow P;Pinter G;Yan W;Wang SE
就像在生态系统中一样，癌症和肿瘤微环境中的其他细胞参与各种相互作用模式，以缓冲环境变化的负面影响。其中一个变化是普通营养素（如谷氨酰胺/Gln）的消耗和随之而来的有毒代谢副产物（如铵/NH 4）的积累。铵是细胞代谢的废物，其积累引起细胞应激。在肿瘤中，已知它可以通过癌症相关成纤维细胞（CAF）再循环为营养物质。在这里，我们提出了单一培养和共培养生长的癌细胞和CAFs上不同的基板：谷氨酰胺和铵。我们提出了一个数学模型来帮助我们理解。我们发现癌细胞能够在铵上存活，并在有限的时间内将其回收为谷氨酰胺。CAF甚至可以在铵上生长。在共培养中，当暴露于铵时，CAF的存在导致癌细胞的存活率比它们的单一培养物提高。有趣的是，两个细胞群体之间的比例在不同浓度的NH 4下保持不变，表明混合细胞系统能够在暂时的代谢应激下存活，并维持作为稳定实体的大小和细胞组成。
Like in an ecosystem, cancer and other cells residing in the tumor microenvironment engage in various modes of interactions to buffer the negative effects of environmental changes. One such change is the consumption of common nutrients (such as glutamine/Gln) and the consequent accumulation of toxic metabolic byproducts (such as ammonium/NH4). Ammonium is a waste product of cellular metabolism whose accumulation causes cell stress. In tumors, it is known that it can be recycled into nutrients by cancer associated fibroblasts (CAFs). Here we present monoculture and coculture growth of cancer cells and CAFs on different substrates: glutamine and ammonium. We propose a mathematical model to aid our understanding. We find that cancer cells are able to survive on ammonium and recycle it to glutamine for limited periods of time. CAFs are able to even grow on ammonium. In coculture, the presence of CAFs results in an improved survival of cancer cells compared to their monoculture when exposed to ammonium. Interestingly, the ratio between the two cell populations is maintained under various concentrations of NH4, suggesting the ability of the mixed cell system to survive temporary metabolic stress and sustain the size and cell composition as a stable entity.
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影响因子：
4.3
作者：
Craig, Morgan;Kaveh, Kamran;Goldman, Aaron
通讯作者：
Goldman, Aaron
影响因子：
4.3
作者：
Lisanti, Michael P.;Martinez-Outschoorn, Ubaldo E.;Sotgia, Federica
通讯作者：
Sotgia, Federica
影响因子：
3.1
作者：
Lagarias, JC;Reeds, JA;Wright, PE
通讯作者：
Wright, PE
细胞外代谢能量可以促进癌症的进展。
影响因子：
64.5
作者：
Loo JM;Scherl A;Nguyen A;Man FY;Weinberg E;Zeng Z;Saltz L;Paty PB;Tavazoie SF
通讯作者：
Tavazoie SF
影响因子：
4.6
作者：
Shamsi M;Saghafian M;Dejam M;Sanati-Nezhad A
通讯作者：
Sanati-Nezhad A