Glutamate involvement in calcium-dependent migration of astrocytoma cells.
Cancer Cell International. 2014-01-01; 14(1): 42
DOI: 10.1186/1475-2867-14-42
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1. Cancer Cell Int. 2014 May 19;14:42. doi: 10.1186/1475-2867-14-42. eCollection
2014.
Glutamate involvement in calcium-dependent migration of astrocytoma cells.
Hamadi A(1), Giannone G(2), Takeda K(1), Rondé P(1).
Author information:
(1)Laboratoire de Biophotonique et Pharmacologie, CNRS, UMR 7213, Université de
Strasbourg, Illkirch 67401, France.
(2)Interdisciplinary Institute for Neuroscience and UMR CNRS 5297, University of
Bordeaux, Bordeaux 33000, France.
BACKGROUND: Astrocytoma are known to have altered glutamate machinery that
results in the release of large amounts of glutamate into the extracellular space
but the precise role of glutamate in favoring cancer processes has not yet been
fully established. Several studies suggested that glutamate might provoke active
killing of neurons thereby producing space for cancer cells to proliferate and
migrate. Previously, we observed that calcium promotes disassembly of
integrin-containing focal adhesions in astrocytoma, thus providing a link between
calcium signaling and cell migration. The aim of this study was to determine how
calcium signaling and glutamate transmission cooperate to promote enhanced
astrocytoma migration.
METHODS: The wound-healing model was used to assay migration of human U87MG
astrocytoma cells and allowed to monitor calcium signaling during the migration
process. The effect of glutamate on calcium signaling was evaluated together with
the amount of glutamate released by astrocytoma during cell migration.
RESULTS: We observed that glutamate stimulates motility in serum-starved cells,
whereas in the presence of serum, inhibitors of glutamate receptors reduce
migration. Migration speed was also reduced in presence of an intracellular
calcium chelator. During migration, cells displayed spontaneous Ca(2+)
transients. L-THA, an inhibitor of glutamate re-uptake increased the frequency of
Ca(2+) oscillations in oscillating cells and induced Ca(2+) oscillations in
quiescent cells. The frequency of migration-associated Ca(2+) oscillations was
reduced by prior incubation with glutamate receptor antagonists or with an
anti-β1 integrin antibody. Application of glutamate induced increases in internal
free Ca(2+) concentration ([Ca(2+)]i). Finally we found that compounds known to
increase [Ca(2+)]i in astrocytomas such as thapsigagin, ionomycin or the
metabotropic glutamate receptor agonist t-ACPD, are able to induce glutamate
release.
CONCLUSION: Our data demonstrate that glutamate increases migration speed in
astrocytoma cells via enhancement of migration-associated Ca(2+) oscillations
that in turn induce glutamate secretion via an autocrine mechanism. Thus,
glutamate receptors are further validated as potential targets for astrocytoma
cancer therapy.
DOI: 10.1186/1475-2867-14-42
PMCID: PMC4032497
PMID: 24860258