Triangular correlation (TrC) between cancer aggressiveness, cell uptake capability, and cell deformability

The malignancy potential is correlated with the mechanical deformability of the cancer cells. However, mechanical tests for clinical applications are limited. We present here a Triangular Correlation (TrC) between cell deformability, phagocytic capacity, and cancer aggressiveness, suggesting that phagocytic measurements can be a mechanical surrogate marker of malignancy. The TrC was proved in human prostate cancer cells with different malignancy potential, and in human bladder cancer and melanoma cells that were sorted into subpopulations based solely on their phagocytic capacity. The more phagocytic subpopulations showed elevated aggressiveness ex vivo and in vivo. The uptake potential was preserved, and differences in gene expression and in epigenetic signature were detected. In all cases, enhanced phagocytic and aggressiveness phenotypes were correlated with greater cell deformability and predicted by a computational model. Our multidisciplinary study provides the proof of concept that phagocytic measurements can be applied for cancer diagnostics and precision medicine.