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

doi:10.1126/sciadv.aax2861

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 journal › Article › peer-review

37 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 language	English
Article number	eaax2861
Journal	Science advances
Volume	6
Issue number	3
DOIs	https://doi.org/10.1126/sciadv.aax2861
State	Published - 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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SDG 3 Good Health and Well-being

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Brill-Karniely, Y., Dror, D., Duanis-Assaf, T., Goldstein, Y., Schwob, O., Millo, T., Orehov, N., Stern, T., Jaber, M., Loyfer, N., Vosk-Artzi, M., Benyamini, H., Bielenberg, D., Kaplan, T., Buganim, Y., Reches, M., & Benny, O. (2020). Triangular correlation (TrC) between cancer aggressiveness, cell uptake capability, and cell deformability. Science advances, 6(3), Article eaax2861. https://doi.org/10.1126/sciadv.aax2861

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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.",

author = "Yifat Brill-Karniely and Dvir Dror and Tal Duanis-Assaf and Yoel Goldstein and Ouri Schwob and Talya Millo and Natalie Orehov and Tal Stern and Mohammad Jaber and Netanel Loyfer and Margarita Vosk-Artzi and Hadar Benyamini and Diane Bielenberg and Tommy Kaplan and Yosef Buganim and Meital Reches and Ofra Benny",

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Brill-Karniely, Y, Dror, D, Duanis-Assaf, T, Goldstein, Y, Schwob, O, Millo, T, Orehov, N, Stern, T, Jaber, M, Loyfer, N, Vosk-Artzi, M, Benyamini, H, Bielenberg, D, Kaplan, T , Buganim, Y , Reches, M & Benny, O 2020, 'Triangular correlation (TrC) between cancer aggressiveness, cell uptake capability, and cell deformability', Science advances, vol. 6, no. 3, eaax2861. https://doi.org/10.1126/sciadv.aax2861

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T1 - Triangular correlation (TrC) between cancer aggressiveness, cell uptake capability, and cell deformability

AU - Brill-Karniely, Yifat

AU - Dror, Dvir

AU - Duanis-Assaf, Tal

AU - Goldstein, Yoel

AU - Schwob, Ouri

AU - Millo, Talya

AU - Orehov, Natalie

AU - Stern, Tal

AU - Jaber, Mohammad

AU - Loyfer, Netanel

AU - Vosk-Artzi, Margarita

AU - Benyamini, Hadar

AU - Bielenberg, Diane

AU - Kaplan, Tommy

AU - Buganim, Yosef

AU - Reches, Meital

AU - Benny, Ofra

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

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