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Sci Adv. 2020 Jan 15;6(3):eaax2861. doi: 10.1126/sciadv.aax2861. eCollection 2020 Jan.

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

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Institute for Drug Research, The School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel.
Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
Info-CORE, Bioinformatics Unit of the I-CORE at the Hebrew University and Hadassah Medical Center, Jerusalem 9112001, Israel.
Department of Surgery, Harvard Medical School, Vascular Biology Program, Boston Children's Hospital, Boston, MA 02115, USA.


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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