Senescent tumor cells building three-dimensional tumor clusters

Scientific Reports
Hyun-Gyu LeeKyoung J Lee

Abstract

Cellular senescence, a permanent cell-cycle arrest, is a common yet intriguing phenomenon, in which its beneficial significance for biological organisms has only begun to be explored. Among others, senescent cells are able to transform tissue structures around them. Tumor cells, whose hallmark is their ability to proliferate indefinitely, are not free from the phenomenon. Here, we report a remarkable observation where senescent cells in a dense mono-layer of breast cancer colony act as aggregating centers for non-senescent cells in their vicinity. Consequently, the senescent cells actively form localized 3D cell-clusters in a confluent 2D tumor layer. The biophysical mechanism underpinning the surprising phenomenon primarily involves mitotic cell-rounding, dynamic and differential cell attachments, and cellular chemotaxis. By incorporating these few biophysical factors, we were able to recapitulate the experimental observation via a cellular Potts Model.

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Citations

Feb 8, 2020·Cells·Francisco Triana-MartínezEduardo Domínguez
Sep 28, 2020·Molecular Oncology·Hui-Ling OuDaniel Muñoz-Espín
May 29, 2021·Clinical and Experimental Pharmacology & Physiology·Da-Yong ZhangWen-Yi Gu
Jul 13, 2021·Frontiers in Oncology·Anindita ChakrabartyGoutam Chowdhury
Sep 24, 2021·PLoS Computational Biology·Hyun Gyu Lee, Kyoung J Lee

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