Triangular correlation (TrC) between cancer aggressiveness, cell uptake capability, and cell deformability
Yifat Brill‐Karniely, Dvir Dror, Tal Duanis‐Assaf, Yoel Goldstein, Ouri Schwob, Talya Millo, Natalie Orehov, Tal Stern, Mohammad Jaber, Netanel Loyfer, Margarita Vosk-Artzi, Hadar Benyamini, Diane R. Bielenberg, Tommy Kaplan, Yosef Buganim, Meital Reches, Ofra Benny
Abstract
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.