Belpomme Dominique, Irigaray Philippe, Alberto Jean-Marc, Poletti Clément, Hinault-Boyer Charlotte, Lacomme Stéphanie
Department of Cancer Clinical Research, Paris V University Hospital, 75015 Paris, France.
European Cancer and Environment Research Institute, 1000 Brussels, Belgium.
Cells. 2025 Jun 19;14(12):931. doi: 10.3390/cells14120931.
We have previously shown that in cancer patients, free methylglyoxal (MG), a side-product of glycolysis, is recovered from tumors at significantly higher levels than from their corresponding non-cancerous tissues. We also recently confirmed our initial experimental finding that in these patients, free MG peripheral blood levels correlate positively with tumor growth, making free MG levels a new metabolic biomarker of tumor growth of interest to detect cancer and clinically follow cancer patients with no available biomarkers. Now we measure free MG and lactate produced by different cancer and normal cells cultured at low or high glucose concentration and in normoxic or hypoxic conditions to question whether cancer cells and non-cancer cells in tumors produce and release free MG and lactate. Surprisingly, we found that normal fibroblastic and endothelial cell lines grown in normoxic conditions produce and release high free MG levels, which we confirmed for non-transformed normal fibroblasts, albeit at significantly lower levels. Cancer cells generally significantly increased their free MG production and release when cultured in high glucose concentration, while normal cells generally did not. Furthermore, in normoxic conditions, normal fibroblastic cells, in addition to free MG, may produce and release lactate. From this data, we propose that in malignant tumors, both cancer and fibroblastic stromal cells may contribute to tumor growth and development by producing via glycolysis both free MG and D-lactate, which, in addition to L-lactate, may be part of the core hallmark of cell metabolic reprogramming in cancer.
我们之前已经表明，在癌症患者中，糖酵解的副产物游离甲基乙二醛（MG）在肿瘤中的回收水平显著高于其相应的非癌组织。我们最近还证实了我们最初的实验发现，即在这些患者中，游离MG外周血水平与肿瘤生长呈正相关，这使得游离MG水平成为一种新的肿瘤生长代谢生物标志物，有望用于检测癌症并对无可用生物标志物的癌症患者进行临床跟踪。现在，我们测量了在低或高葡萄糖浓度以及常氧或低氧条件下培养的不同癌细胞和正常细胞产生的游离MG和乳酸，以探究肿瘤中的癌细胞和非癌细胞是否产生并释放游离MG和乳酸。令人惊讶的是，我们发现常氧条件下生长的正常成纤维细胞系和内皮细胞系会产生并释放高水平的游离MG，我们对未转化的正常成纤维细胞也证实了这一点，尽管水平明显较低。癌细胞在高葡萄糖浓度下培养时，其游离MG的产生和释放通常会显著增加，而正常细胞通常不会。此外，在常氧条件下，正常成纤维细胞除了产生游离MG外，还可能产生并释放乳酸。根据这些数据，我们提出，在恶性肿瘤中，癌细胞和成纤维基质细胞可能都通过糖酵解产生游离MG和D-乳酸，从而促进肿瘤的生长和发展，除了L-乳酸外，这两者可能是癌症细胞代谢重编程核心特征的一部分。
