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

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