Metabolic alterations in lung cancer-associated fibroblasts correlated with increased glycolytic metabolism of the tumor.
Metabolic alterations in lung cancer-associated fibroblasts correlated with increased glycolytic metabolism of the tumor.
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DOI：
10.1158/1541-7786.mcr-12-0437-t
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发表时间：
2013-06
期刊：
影响因子：
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通讯作者：
McGraw TE
中科院分区：
文献类型：
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作者：
Chaudhri VK;Salzler GG;Dick SA;Buckman MS;Sordella R;Karoly ED;Mohney R;Stiles BM;Elemento O;Altorki NK;McGraw TE
癌细胞经历代谢重编程，但对肿瘤内其他细胞的代谢改变知之甚少。我们使用基于质谱的分析和基于代谢途径的系统分析来比较21个原发性人肺癌癌相关成纤维细胞系（CAF）与从相邻非肿瘤肺组织产生的“正常”成纤维细胞系（NF）。CAF具有促肿瘤作用，尽管CAF支持肿瘤的机制尚未阐明。我们已经确定了几个途径，其代谢物丰度在全球范围内将CAFs与NF区分开来，这表明代谢改变不仅限于癌细胞。此外，我们发现来自高和低糖酵解肿瘤的CAFs之间的代谢差异，这可能反映了CAFs与肿瘤糖酵解能力相关的不同作用。其中一个变化是CAF中二肽的增加。二肽主要来自蛋白质的分解。我们发现在CAFs中，基础大自噬增加，这可能是二肽增加的原因。此外，我们证明了CAFs和NF之间的差异，在诱导减少葡萄糖促进自噬。总之，我们的数据表明，增加的自噬可以解释CAFs和NF之间的代谢差异，并可能在肺癌中发挥额外的尚未确定的作用。
Cancer cells undergo a metabolic reprogramming but little is known about metabolic alterations of other cells within tumors. We use mass spectrometry-based profiling and a metabolic pathway-based systems analysis to compare 21 primary human lung tumor cancer-associated fibroblast lines (CAFs) to “normal” fibroblast lines (NFs) generated from adjacent non-neoplastic lung tissue. CAFs are pro-tumorigenic, although the mechanisms by which CAFs support tumors have not been elucidated. We have identified several pathways whose metabolite abundance globally distinguished CAFs from NFs, suggesting that metabolic alterations are not limited to cancer cells. In addition, we found metabolic differences between CAFs from high and low glycolytic tumors that might reflect distinct roles of CAFs related to the tumor’s glycolytic capacity. One such change was an increase of dipeptides in CAFs. Dipeptides primarily arise from the breakdown of proteins. We found in CAFs an increase in basal macroautophagy which likely accounts for the increase in dipeptides. Furthermore, we demonstrate a difference between CAFs and NFs in the induction of autophagy promoted by reduced glucose. In sum, our data suggest increased autophagy may account for metabolic differences between CAFs and NFs and may play additional as yet undetermined roles in lung cancer.