Glucose Regulates Calcium Dynamics in Human Metastatic Cells

Cancer cells exhibit an increased dependence on aerobic glycolysis, known as the “Warburg Effect,” leading to increased glucose metabolism that is associated with increased cell proliferation. Intracellular calcium ([Ca²⁺]ⁱⁿ) is also  involved in the regulation of signaling pathways that lead to cell growth, differentiation and metastasis.  In this study, we investigated the interaction between glucose and calcium dynamics in human prostate cancer cells with distinct metastatic potential. Highly (CL-1, CL-2, DU145) and lowly (LNCaP) metastatic prostate cancer cells were intracellularly loaded with the fluorescent calcium indicator Fluo-4. The Ca²⁺ signals of single cells were captured by CCD cameras in the millisecond time frame and analyzed using Metafluor imaging software. Cells were stimulated with ATP that binds to purinergic receptors and triggers Ca²⁺ oscillations. These experiments were done in the presence and absence of glucose, where cells were deprived of glucose for defined periods of time.  Experiments were also performed in the presence and absence of extracellular Ca²⁺. We concluded that in the presence of glucose highly metastatic cells exhibit Ca²⁺ oscillations that were higher in amplitude and frequency in DU145> CL-2> CL-1, whereas LNCaP did not exhibit any response. The absence of glucose decreased the amplitude and frequency of the Ca²⁺oscillations in a time dependent manner. Other carbon sources such as glutamine rescue the Ca²⁺ oscillations in glucose deprived cells. These data indicate that glucose metabolism is required for the maintenance of Ca²⁺ oscillation in highly metastatic cells, and suggest that targeting glucose metabolism could be used to halt metastasis.