Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release

Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release

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 an...

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Bibliographic Details
Published in:International journal of oncology Vol. 39; no. 2; pp. 453 - 463
Main Authors: GOETZE, Kristina, WALENTA, Stefan, KSLAZKIEWICZ, Magdalena, KUNZ-SCHUGHART, Leoni A, MUELLER-KLIESER, Wolfgang
Format: Journal Article
Language:English
Published: Athens Editorial Academy of the International Journal of Oncology 01-08-2011
Subjects:
Biological and medical sciences
Cell Line, Tumor
Cell Movement - drug effects
Cytokines - secretion
Humans
Integrin beta Chains - metabolism
Lactic Acid - pharmacology
Medical sciences
Monocytes - drug effects
Monocytes - metabolism
Neoplasms - metabolism
Tumors
monocytes
Monocyte
Cytokine
Microenvironment
Lactates
Cell motility
Cancerology
Tumor
Inhibitor
cytokines
Lactic acid
lactate
Tumor cell
Cell migration
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Summary: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.
ISSN:1019-6439
1791-2423
DOI:10.3892/ijo.2011.1055