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 Bielenberg, Tommy Kaplan, Yosef Buganim, Meital Reches, Ofra Benny

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageAmerican English
Article numbereaax2861
JournalScience advances
Volume6
Issue number3
DOIs
StatePublished - 2020

Bibliographical note

Funding Information:
We thank The Crown Genomics institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science for RNA sequencing and G. Friedlander, Mantoux Bioinformatics Institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, for analyzing the RNA sequence. We thank N. Melamed-Book from the Bio-Imaging Unit of The Hebrew University of Jerusalem for assistance with time-lapse confocal imaging. Funding: This project received funding from the European Research Council (ERC-StG) under the European Union?s Horizon 2020 research and innovation program (grant agreement no. 0305260). We thank the Israel Ministry of Science and Technology (MOST) (grant agreement no. 0394906) and the Israel Science Foundation (grant agreement no. 0394883) for funding and the Teacher-Scholars program of The Hebrew University of Jerusalem supported by

Publisher Copyright:
Copyright © 2020 The Authors

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