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Intracellular calcium oscillations in strongly metastatic human breast and prostate cancer cells: control by voltage-gated sodium channel activity

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Abstract

The possible association of intracellular Ca2+ with metastasis in human cancer cells is poorly understood. We have studied Ca2+ signaling in human prostate and breast cancer cell lines of strongly versus weakly metastatic potential in a comparative approach. Intracellular free Ca2+ was measured using a membrane-permeant fluorescent Ca2+-indicator dye (Fluo-4 AM) and confocal microscopy. Spontaneous Ca2+ oscillations were observed in a proportion of strongly metastatic human prostate and breast cancer cells (PC-3M and MDA-MB-231, respectively). In contrast, no such oscillations were observed in weakly/non metastatic LNCaP and MCF-7 cells, although a rise in the resting Ca2+ level could be induced by applying a high-K+ solution. Various parameters of the oscillations depended on extracellular Ca2+ and voltage-gated Na+ channel activity. Treatment with either tetrodotoxin (a general blocker of voltage-gated Na+ channels) or ranolazine (a blocker of the persistent component of the channel current) suppressed the Ca2+ oscillations. It is concluded that the functional voltage-gated Na+ channel expression in strongly metastatic cancer cells makes a significant contribution to generation of oscillatory intracellular Ca2+ activity. Possible mechanisms and consequences of the Ca2+ oscillations are discussed.

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Acknowledgments

We would like to acknowledge continued financial support from the Pro Cancer Research Fund (PCRF) in the form of a rolling grant (MBAD, SPF). RO was supported by the British Heart Foundation (BHF).

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Authors and Affiliations

  1. Department of Life Sciences, Neuroscience Solutions to Cancer Research Group, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK

    Nahit Rizaner, Rustem Onkal, Scott P. Fraser & Mustafa B. A. Djamgoz

  2. Biotechnology Research Centre, Cyprus International University, Haspolat, Mersin, Turkey

    Nahit Rizaner, Rustem Onkal & Mustafa B. A. Djamgoz

  3. Department of Life Sciences, Sir Ernst Chain Building, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK

    Alessandro Pristerá & Kenji Okuse

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  1. Nahit Rizaner
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Correspondence to Nahit Rizaner.

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MBAD has a patent pending for use of blockers of the persistent component of the voltage-gated sodium channel as anti-cancer agents.

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Special Issue: Ion Channels, Transporters and Cancer.

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Rizaner, N., Onkal, R., Fraser, S.P. et al. Intracellular calcium oscillations in strongly metastatic human breast and prostate cancer cells: control by voltage-gated sodium channel activity. Eur Biophys J 45, 735–748 (2016). https://doi.org/10.1007/s00249-016-1170-x

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