Glutamate involvement in calcium–dependent migration of astrocytoma cells

Cancer Cell International

Philippe Rondé¹  Kenneth Takeda¹  Grégory Giannone²  Abdelkader Hamadi¹ 

[1] Laboratoire de Biophotonique et Pharmacologie, CNRS, UMR 7213, Université de Strasbourg, Illkirch 67401, France;Interdisciplinary Institute for Neuroscience and UMR CNRS 5297, University of Bordeaux, Bordeaux 33000, France

关键词: Calcium spikes;    U-87MG cell;    Migration;    Glutamate release;   

Others  :  791988
DOI  :  10.1186/1475-2867-14-42

 received in 2013-12-12, accepted in 2014-04-30,  发布年份 2014

【 摘 要 】

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 Ca²⁺ transients. L-THA, an inhibitor of glutamate re-uptake increased the frequency of Ca²⁺ oscillations in oscillating cells and induced Ca²⁺ oscillations in quiescent cells. The frequency of migration-associated Ca²⁺ 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 Ca²⁺ concentration ([Ca²⁺]_i). Finally we found that compounds known to increase [Ca²⁺]_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 Ca²⁺ oscillations that in turn induce glutamate secretion via an autocrine mechanism. Thus, glutamate receptors are further validated as potential targets for astrocytoma cancer therapy.

【 授权许可】

   
2014 Hamadi et al.; licensee BioMed Central Ltd.

【 图 表 】

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