Characteristic shape and surface changes in epithelial transformation

Abstract

Previous work has suggested that adhesive or cytoskeletal structures alter during epithelial transformation. The purpose of the present studies was to see whether such reorganizations were accompanied by consistent changes in the biophysical characteristics of cells. We used in vitro cell lines from rat liver and respiratory tract epithelium that became tumorigenic over a period of 11–15 months. For populations sampled at several time points before and after this transition, the shape of individual cells was analysed by calculating the values of many geometrical descriptors. The data were collected from cells imaged by reflected light interference. Interference contours on the cells were digitized, and the descriptor values calculated by computer program. Cell lines derived from both liver (IAR 20PC1) and respiratory epithelium (1000 W) lines showed progressive changes in the values of certain descriptors. The time-dependent differences among groups were statistically significant at a level of p < 0.0001. By determining which descriptors underwent large changes, we found that some structural revisions occurred in common in the two types of cells. Cells from later passages of the lines rose from the substrate at a steeper angle, as determined by measuring the fraction of the area of the first interference contour that was occupied by successive contours. In addition, the projections on the perimeter became broader, and the perimeter became less complex. This kind of ‘smoothing’ of the cell perimeter took place in several contours, indicating that it was a surface change. Surface changes of this sort have not been noted previously in transformation. The results suggest that the structure of cells is altered in a consistent way during transformation, as detected by measuring of shape and surface configuration.