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

• Published in: European biophysics journal Vol. 45; no. 7; pp. 735 - 748
• Main Authors: Rizaner, Nahit, Onkal, Rustem, Fraser, Scott P., Pristerá, Alessandro, Okuse, Kenji, Djamgoz, Mustafa B. A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2016; Springer Nature B.V
• Subjects: Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Breast cancer; Breast Neoplasms - pathology; Calcium; Calcium Signaling; Cell Biology; Extracellular Space - metabolism; Gene Expression Regulation, Neoplastic; Humans; Intracellular Space - metabolism; Life Sciences; Male; MCF-7 Cells; Membrane Biology; Metastasis; Nanotechnology; Neoplasm Metastasis; Neurobiology; Original Article; Prostate cancer; Prostatic Neoplasms - pathology; Sodium; Voltage-Gated Sodium Channels - metabolism; Persistent current; Tetrodotoxin; Calcium oscillation; Metastasis; Voltage-gated sodium channel; Ranolazine
• ISSN: 0175-7571; 1432-1017
• DOI: 10.1007/s00249-016-1170-x

The possible association of intracellular Ca 2+ with metastasis in human cancer cells is poorly understood. We have studied Ca 2+ signaling in human prostate and breast cancer cell lines of strongly versus weakly metastatic potential in a comparative approach. Intracellular free Ca 2+ was measured using a membrane-permeant fluorescent Ca 2+ -indicator dye (Fluo-4 AM) and confocal microscopy. Spontaneous Ca 2+ 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 Ca 2+ level could be induced by applying a high-K + solution. Various parameters of the oscillations depended on extracellular Ca 2+ 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 Ca 2+ 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 Ca 2+ activity. Possible mechanisms and consequences of the Ca 2+ oscillations are discussed.