乳酸：肿瘤代谢中的关键调控者

Lactate: a metabolic key player in cancer

　

癌症研究.2011年11月15日;71(22):6921-5。doi: 10.1158 / 0008 - 5472. - 11 - 1457。

hschhaeuser F1, Sattler UG, Mueller-Klieser W.

德国美因茨约翰内斯古登堡大学医学中心生理学和病理生理学研究所。

摘要
即使在常氧条件下，癌细胞增加葡萄糖的摄取和乳酸的积累。有氧糖酵解或Warburg效应)，是癌细胞的一个共同特征。这一现象清楚地表明乳酸 是肿瘤缺氧的替代物。肿瘤乳酸可以预测转移和患者的总体生存，这是由几项不同实体的研究显示的。肿瘤的转移是通过肿瘤相关成纤维细胞分泌乳酸诱导的透明质酸促进的，这为转移创造了有利的环境。乳酸本身可以诱导细胞和细胞簇的迁移。此外，辐射抗性与乳酸浓度呈正相关，提示乳酸具有抗氧化能力。肿瘤代谢物与免疫细胞相互作用的研究结果表明，乳酸参与了免疫逃逸。此外，乳酸在伤口愈合、慢性炎症和癌症的发展之间架起了桥梁。肿瘤细胞通过乳酸诱导的VEGF分泌，确保有足够的氧气和营养供应，促进增殖，从而形成新的血管。总之，在实体肿瘤中乳酸的积累是恶性肿瘤发展的关键和早期事件。乳酸的测定应进入进一步的临床试验，以确定其在癌症生物学中的相关性。

Cancer Res. 2011 Nov 15;71(22):6921-5. doi: 10.1158/0008-5472.CAN-11-1457.
Lactate: a metabolic key player in cancer.
Hirschhaeuser F1, Sattler UG, Mueller-Klieser W.
Author information
1
Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Abstract
Increased glucose uptake and accumulation of lactate, even under normoxic conditions (i.e., aerobic glycolysis or the Warburg Effect), is a common feature of cancer cells. This phenomenon clearly indicates that lactate is not a surrogate of tumor hypoxia. Tumor lactate can predict for metastases and overall survival of patients, as shown by several studies of different entities. Metastasis of tumors is promoted by lactate-induced secretion of hyaluronan by tumor-associated fibroblasts that create a milieu favorable for migration. Lactate itself has been found to induce the migration of cells and cell clusters. Furthermore, radioresistance has been positively correlated with lactate concentrations, suggesting an antioxidative capacity of lactate. Findings on interactions of tumor metabolites with immune cells indicate a contribution of lactate to the immune escape. Furthermore, lactate bridges the gap between high lactate levels in wound healing, chronic inflammation, and cancer development. Tumor cells ensure sufficient oxygen and nutrient supply for proliferation through lactate-induced secretion of VEGF, resulting in the formation of new vessels. In summary, accumulation of lactate in solid tumors is a pivotal and early event in the development of malignancies. The determination of lactate should enter further clinical trials to confirm its relevance in cancer biology.

　

参考文献：

Lactate: a metabolic key player in cancer. - PubMed - NCBI https://www.ncbi.nlm.nih.gov/pubmed/22084445