Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release.
Kristina Goetze,Stefan Walenta,Magdalena Ksiazkiewicz,Leoni A. Kunz-Schughart,Wolfgang Mueller-Klieser +4 more
TLDR
It is shown here that lactate enhances tumor cell motility of head and neck carcinoma cell lines significantly in a dose-dependent manner and promotes tumor progression by contributing to the phenomenon of tumor immune escape and by enhancing the migratory potential of the malignant cell population.Abstract:
In solid malignant tumors, lactate has been identified as a prognostic parameter for metastasis and overall survival of patients. To investigate the effects of lactate on tumor cell migration, Boyden chamber assays were applied. We could show here that lactate enhances tumor cell motility of head and neck carcinoma cell lines significantly in a dose-dependent manner. The changes in tumor cell migration could be attributed to L-lactate or a conversion of lactate to pyruvate, as only these two substances were able to increase migration. Addition of D-lactate or changes in osmolarity or intracellular pH did not alter the migratory potential of the cells investigated. Because lactate was shown earlier to impair the penetration of dendritic cells in a tumor spheroid model, which is contrary to the response of the malignant cell population in the present study, we included blood monocytes in our assay as a highly motile immune cell type and precursor of tumor-associated macrophages. Interestingly, high levels of L-lactate (20 mM) at a pH of 7.4 inhibited monocyte migration in the Boyden chamber system. In addition, cytokine release of TNF and IL-6 was inhibited. The obtained data suggest that high lactate content promotes tumor progression by contributing to the phenomenon of tumor immune escape and by enhancing the migratory potential of the malignant cell population which may directly be coupled to a higher incidence of metastasis.read more
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The Emerging Hallmarks of Cancer Metabolism
TL;DR: This Perspective has organized known cancer-associated metabolic changes into six hallmarks: deregulated uptake of glucose and amino acids, use of opportunistic modes of nutrient acquisition, useof glycolysis/TCA cycle intermediates for biosynthesis and NADPH production, increased demand for nitrogen, alterations in metabolite-driven gene regulation, and metabolic interactions with the microenvironment.
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Acidic extracellular microenvironment and cancer
Yasumasa Kato,Shigeyuki Ozawa,Chihiro Miyamoto,Yojiro Maehata,Atsuko Suzuki,Toyonobu Maeda,Yuh Baba +6 more
TL;DR: CO2 from the pentose phosphate pathway is an alternative source of acidity, showing that hypoxia and extracellular acidity are, while being independent from each other, deeply associated with the cellular microenvironment.
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Lactate: a metabolic key player in cancer.
TL;DR: Accumulation of lactate in solid tumors is a pivotal and early event in the development of malignancies and should enter further clinical trials to confirm its relevance in cancer biology.
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The Science and Translation of Lactate Shuttle Theory
TL;DR: Clinical studies are utilizing lactate to treat pro-inflammatory conditions and to deliver optimal fuel for working muscles in sports medicine and "Lactate shuttle" concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signaling.
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Reexamining cancer metabolism: lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect
TL;DR: It is posited that in carcinogenesis, aberrant cell signaling due to exaggerated and continually high lactate levels yields an inappropriate positive feedback loop that increases glucose uptake, glycolysis, lactate production and release, decreases mitochondrial function and clearance and upregulates glyCOlytic enzyme and monocarboxylate transporter expression thereby supporting angiogenesis, immune escape, cell migration, metastasis and self-sufficient metabolism.
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