Publication: ATP stimulates chemokine production via a store-operated calcium entry pathway in C6 glioma cells
Issued Date
2009-12-15
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ISSN
14712407
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2-s2.0-74549117714
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Mahidol University
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SCOPUS
Bibliographic Citation
BMC Cancer. Vol.9, (2009)
Suggested Citation
Nattinee Jantaratnotai, Hyun B. Choi, James G. McLarnon ATP stimulates chemokine production via a store-operated calcium entry pathway in C6 glioma cells. BMC Cancer. Vol.9, (2009). doi:10.1186/1471-2407-9-442 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/27097
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Title
ATP stimulates chemokine production via a store-operated calcium entry pathway in C6 glioma cells
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Abstract
Background: Glioma present as one of the most challenging cancers to treat, however, understanding of tumor cell biology is not well understood. Extracellular adenosine triphosphate (ATP) could serve as a critical signaling molecule regulating tumor development. This study has examined pharmacological modulation of calcium (Ca2+) entry through store-operated channels (SOC) on cellular expression and production of immune-cell mobilizing chemokines in ATP-stimulated C6 glioma cells.Methods: Calcium spectrofluorometry was carried out to measure mobilization of intracellular Ca2+ [Ca2+]i following ATP stimulation of rat C6 glioma cells. Pretreatment with two inhibitors of SOC, SKF96365 or gadolinium, was used to examine for effects on [Ca2+]i. RT-PCR was performed to determine effects of purinergic stimulation on C6 cell expression of metabotropic P2Y receptors (P2YR) and the chemokines, monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8). ELISA was carried out to measure production of MCP-1 and IL-8 with ATP stimulation of glioma cells.Results: Application of ATP (at 100 μM) to C6 glioma induced an increase in [Ca2+]i with the response exhibiting two components of decay. In the presence of the SOC inhibitors, SKF96365 or gadolinium, or with Ca2+-free solution, ATP responses lacked a slow phase suggesting the secondary component was due to SOC-mediated influx of Ca2+. RT-PCR confirmed expression of purinergic P2Y-subtype receptors in C6 cells which would serve as a precursor to activation of SOC. In addition, ATP-stimulated C6 cells showed enhanced expression of the chemokines, MCP-1 and IL-8, with SKF96365 or gadolinium effective in reducing chemokine expression. Gadolinium treatment of ATP-stimulated C6 cells was also found to inhibit the production of MCP-1 and IL-8.Conclusion: These results suggest ATP-induced Ca2+ entry, mediated by activation of SOC in C6 glioma, as a mechanism leading to increased cellular expression and release of chemokines. Elevated levels of MCP-1 and IL-8 are predicted to enhance the mobility of tumor cells and promote recruitment of microglia into developing tumors thereby supporting tumor growth. © 2009 Jantaratnotai et al; licensee BioMed Central Ltd.