A Potential Model for Detecting Crowding-induced Epithelial Cell and Cancer Cell Extrusion

Abstract

Overcrowding and cell deformation lead to the shedding of apoptotic and live cells to maintain homeostasis in the epithelium. Recent studies have attempted to explain the effect of extrusion on epithelial homeostasis and tumor metastasis, but lack the requisite quantitative models for testing extrusion. Here, we designed a petri dish inversion model to detect the extrusion ability of both normal epithelial cells and epithelial cancer cells. Firstly, we found cell extrusion was observed in both normal epithelial cells (LO2 cells) and cancer cells; in confluent LO2 cell culture, certain cells were surrounded by their neighbors, suffered "collective attack", and were then made round in shape. Green fluorescent protein (GFP)-labeled cancer cells were also found to be squeezed by normal LO2 cells. Using the petri dish inversion model, we quantified the number of extrusion cells, and demonstrated that the ability of cancer cell extrusion was related to the metastatic potential of cancer cell lines. Our findings provide a novel model to detect crowding-induced epithelial cell and cancer cell extrusion. This novel model provides a quantitative method for research into apoptotic and cancer cell extrusion, particularly in human hepatocellular carcinoma.