Morpho-physiological heterogeneity of cells within two rat prostate carcinoma cell lines AT-2 and MAT-LyLu differing in the degree of malignancy observed by cell cloning and the effects of caffeine, theophylline and papaverine upon a proportion of the clones.

Analysis of the heterogeneity of clones of single cells from two established lines of the Dunning series of rat prostate carcinoma differing in the degree of malignancy, AT-2 (moderately malignant) and MAT-LyLu (highly malignant), was conducted. The results showed that not only the original tumors and primary cell cultures were heterogeneous but also the established cell lines of tumor origin. In the MAT-LyLu cell line, the clones of cells with morpho-physiological features characteristic of malignant cells dominated, whereas diverse types of clones were present in the AT-2 cell line. Differences in cell morphology (EMT), multi-layering and release from contact inhibition followed by active migration were observed and found to be correlated with increased expression of proteins involved in cancer cell invasiveness: connexin 43 and transcription factor Snail. Caffeine, theophylline and papaverine, reported to show anticancer activity in vivo, were found to decrease the proportion of clones displaying malignant cell features in the AT-2 cell line. At the tested concentrations, these compounds reversibly retarded cell growth but did not inhibit it. The results showed that the heterogeneity of cell populations within the cell lines should be taken into account in experiments carried out in vitro on established model cancer cell lines.