Random nature of epithelial cancer cell monolayers

Although the polygonal shape of epithelial cells has been drawing the attention of scientists for several centuries, only a decade and a half ago it was demonstrated that distributions of polygon types (DOPTs) are similar in proliferative epithelia of many different plant and animal species. In this study, we show that hyper-proliferation of cancer cells disrupts this universal paradigm and results in randomly organized epithelial structures. Examining non-synchronized and synchronized HeLa cervix cells, we suppose that the spread of cell sizes is the main parameter controlling the DOPT in the cancer cell monolayers. To test this hypothesis, we develop a theory of morphologically similar random polygonal packings. By analysing differences between tumoural and normal epithelial cell monolayers, we conclude that the latter have more ordered structures because of their lower proliferation rates and, consequently, more effective relaxation of mechanical stress associated with cell division and growth. To explain the structural features of normal proliferative epithelium, we take into account the spread of cell sizes in the monolayer. The proposed theory also rationalizes some highly ordered unconventional post-mitotic epithelia.