Heat Stress-Induced Multiple Multipolar Divisions of Human Cancer Cells.

Chen Chen,Feng Feng,Liu Liu,Huang Huang,Li Li,Zhao Zhao

doi:10.3390/cells8080888

Abstract

Multipolar divisions of heated cells has long been thought to stem from centrosome aberrations of cells directly caused by heat stress. In this paper, through long-term live-cell imaging, we provide direct cellular evidences to demonstrate that heat stress can promote multiple multipolar divisions of MGC-803 and MCF-7 cells. Our results show that, besides facilitating centrosome aberration, polyploidy induced by heat stress is another mechanism that causes multipolar cell divisions, in which polyploid cancer cells engendered by mitotic slippage, cytokinesis failure, and cell fusion. Furthermore, we also find that the fates of theses polyploid cells depend on their origins, in the sense that the polyploid cells generated by mitotic slippage experience bipolar divisions with a higher rate than multipolar divisions, while those polyploid cells induced by both cytokinesis failure and cell fusion have a higher frequency of multipolar divisions compared with bipolar divisions. This work indicates that heat stress-induced multiple multipolar divisions of cancer cells usually produce aneuploid daughter cells, and might lead to genetically unstable cancer cells and facilitate tumor heterogeneity.

Highlights

Normal bipolar mitosis in eukaryotic cells is an essential process in the development of tissues and organs
Our results show that MGC-803 cells and MCF-7 cells with heat stress treatment can exhibit mitotic slippage, cytokinesis failure, cell fusion, and centrosomes aberrations simultaneously, producing multiple multipolar divisions
Our experiments demonstrate that heat stress can directly induce centrosome aberrations, thereby leading to multipolar divisions of cancer cells

Summary

Introduction

Normal bipolar mitosis in eukaryotic cells is an essential process in the development of tissues and organs. It maintains genomic stability by establishing bipolar spindles with an accurate centrosome number and centrosome structure during cell division, and executes precise segregation of chromosomes, centrosomes, cytoplasm, and organelles during the mitosis for mammalian cells. Multipolar cell division can be promoted by polyploid cells [7], and various treatments by paclitaxel [8], colchicine [9], carboplatin [10], confined microenvironment [11,12], UV- and. Temme et al [14] found that the fraction of dividing cells that exhibited multipolar divisions was elevated to about 50% in the heated Chinese hamster ovary (CHO) cells.

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