Phosphorescence-based oxygen sensing reveals size-dependent survival and motility of metastatic prostate cancer cells in severely hypoxic conditionsNew Submission

Cancer cells in solid tumors exist under conditions of low self-generated oxygen concentration, known as hypoxia, as the tumor oxygen demand exceeds the oxygen supply provided by the surrounding vasculature. However, it is unclear how these cancer cells adapt to such environmental stress. Here, we use a transparent phosphorescent thin film to visualize the self-generated hypoxia field of confluent metastatic PC3 cancer cells. The single-cell tracked movement of cells in steep hypoxia gradients shows a bias of larger cells migrating toward higher oxygen concentrations. Removal of severe hypoxia before apoptosis shows that the surviving population of cells is biased toward cells with larger areas. Furthermore, we show that, if allowed to progress too long, self-induced hypoxia generates apoptotic blebbing of cells, predominantly producing large cells as survivors. In general, the distributions of the cell area of cancer cells as they descend and recover from severe self-generated hypoxia reveal that larger cancer cells maintain their metabolism for a longer period than smaller cells. Under the hypothesis that the largest PC3 cells are polyaneuploid, our findings suggest the enhanced metabolic fitness of polyaneuploid cells under extreme hypoxia, and identify these larger cells as a potential target for cancer therapy.