Tumor Cell Fusion and Multipolar Trivision

Abstract

The fusogenic character of tumor cells has been suspected, without direct visualization of such processes. Fusion is likely to create polyploid cells, instability, chromosome loss, and induce tumorigenicity. The aim of this study was to provide direct evidence for the fusion and trivision of hyperploid tumor cells and their viability. Cell fusion was captured by time-lapse microscopy in hypertriploid (> 3N) HeLa cell culture followed by trivisions and seen with relatively high frequency (1:24, 4%) relative to cell divisions. The diameters of round M phase HeLa, HaCaT and uveal melanoma cells and their cell volumes before trivision were significantly larger than the size of cells to be divided, while the average volumes of trivided cells were smaller than divided cells. The volume of trivided smaller cells was not uniform indicating an uneven distribution of cytoplasmic material. We provide cinemicrophotographic evidence that after fusion the hybrid HeLa cell undergoes trivision and generates one large and two smaller cells. In the next cell cycle the larger daughter cell divides in two cells, the two smaller daughter cells fuse and trivide. Fused hybrid tumor cells are viable and generate further trivisions and divisions conforming to the cell fusion hypothesis suggesting that fusion generates aneuploid small tumor cells that can lead to metastasis.