Tumor - endothelial cell interaction and glucose metabolism



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Metastasis involves cell invasion and cell migration. The tumor cells which disseminate from their primary organ need to intravasate and extravasate to colonize new organs and tissues. To do this, the tumor cells must interact with the endothelial cells lining the blood vessels. The mechanisms involved in these interactions are poorly understood. We hypothesise that the physical interaction between tumor and endothelial cells would increase intracellular calcium in both endothelial and tumor cells. To address this, we developed a cell separator chamber that allows coronary microvascular endothelial cells and tumor cells to grow side by side. The intracellular calcium in these cells was determined using Fura-2, a Ca2+ indicator and ion ratio imaging micrscopy. We showed that metastatic cells elicit calcium oscillations upon simulation with nanomolar concentrations of ATP, but that endothelial cells do not when stimulated at these same concentrations. More importantly, when endothelial cells are grown with metastatic cells, they responded with an increase in intracellular calcium when stimulated by nanomolar concentrations of ATP. Our data also indicated that interaction between endothelial and metastatic cells elicited larger ATP-induced increases in cytosolic Ca2+([Ca2+]cyt) in both cell types. These results suggest that tumor and endothelial cells communicate via calcium signaling. This has signficance, because intracellular calcium is involved in many steps needed for metastasis such as cell migration and cell invasion and for intra- and extra-vasation to colonize distant organs.



Calcium, Cell Interaction