Lactate: a metabolic key player in cancer - PubMed (original) (raw)
Review
Lactate: a metabolic key player in cancer
Franziska Hirschhaeuser et al. Cancer Res. 2011.
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.
©2011 AACR
Similar articles
- Pyruvate into lactate and back: from the Warburg effect to symbiotic energy fuel exchange in cancer cells.
Feron O. Feron O. Radiother Oncol. 2009 Sep;92(3):329-33. doi: 10.1016/j.radonc.2009.06.025. Epub 2009 Jul 13. Radiother Oncol. 2009. PMID: 19604589 Review. - Lactate: mirror and motor of tumor malignancy.
Walenta S, Mueller-Klieser WF. Walenta S, et al. Semin Radiat Oncol. 2004 Jul;14(3):267-74. doi: 10.1016/j.semradonc.2004.04.004. Semin Radiat Oncol. 2004. PMID: 15254870 Review. - Tumor lactate content predicts for response to fractionated irradiation of human squamous cell carcinomas in nude mice.
Quennet V, Yaromina A, Zips D, Rosner A, Walenta S, Baumann M, Mueller-Klieser W. Quennet V, et al. Radiother Oncol. 2006 Nov;81(2):130-5. doi: 10.1016/j.radonc.2006.08.012. Epub 2006 Sep 14. Radiother Oncol. 2006. PMID: 16973228 - Tumor metabolism as modulator of immune response and tumor progression.
Gottfried E, Kreutz M, Mackensen A. Gottfried E, et al. Semin Cancer Biol. 2012 Aug;22(4):335-41. doi: 10.1016/j.semcancer.2012.02.009. Epub 2012 Mar 3. Semin Cancer Biol. 2012. PMID: 22414910 Review. - Hypothesis: using the Warburg effect against cancer by reducing glucose and providing lactate.
Nijsten MW, van Dam GM. Nijsten MW, et al. Med Hypotheses. 2009 Jul;73(1):48-51. doi: 10.1016/j.mehy.2009.01.041. Epub 2009 Mar 4. Med Hypotheses. 2009. PMID: 19264418
Cited by
- Glycolysis-related gene induction and ATP reduction during fractionated irradiation. Markers for radiation responsiveness of human tumor xenografts.
Goetze K, Meyer SS, Yaromina A, Zips D, Baumann M, Mueller-Klieser W. Goetze K, et al. Strahlenther Onkol. 2013 Sep;189(9):782-8. doi: 10.1007/s00066-013-0371-9. Epub 2013 Jul 6. Strahlenther Onkol. 2013. PMID: 23828461 - Nanomicellar Formulation of Clotrimazole Improves Its Antitumor Action toward Human Breast Cancer Cells.
Marcondes MC, Fernandes AC, Itabaiana I Jr, de Souza RO, Sola-Penna M, Zancan P. Marcondes MC, et al. PLoS One. 2015 Jun 22;10(6):e0130555. doi: 10.1371/journal.pone.0130555. eCollection 2015. PLoS One. 2015. PMID: 26098874 Free PMC article. - Osthole increases the radiosensitivity of hepatoma cells by inhibiting GSK-3β/AMPK/mTOR pathway-controlled glycolysis.
Huang H, Xue J, Xie T, Xie ML. Huang H, et al. Naunyn Schmiedebergs Arch Pharmacol. 2023 Apr;396(4):683-692. doi: 10.1007/s00210-022-02347-8. Epub 2022 Nov 29. Naunyn Schmiedebergs Arch Pharmacol. 2023. PMID: 36445387 - The Metabolic Heterogeneity and Flexibility of Cancer Stem Cells.
Tanabe A, Sahara H. Tanabe A, et al. Cancers (Basel). 2020 Sep 28;12(10):2780. doi: 10.3390/cancers12102780. Cancers (Basel). 2020. PMID: 32998263 Free PMC article. Review. - Lactate levels with glioblastoma multiforme.
Kahlon AS, Alexander M, Kahlon A, Wright J. Kahlon AS, et al. Proc (Bayl Univ Med Cent). 2016 Jul;29(3):313-4. doi: 10.1080/08998280.2016.11929449. Proc (Bayl Univ Med Cent). 2016. PMID: 27365883 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous