Autoselection Phenomenon in the Normal Cell Clone Undergoing Differentiation: From Cell Population Heterogeneity to Cancer Phenotype via Nonmutational Changes

Abstract

The problern of regulation of the proliferation-differentiation processes is analysed in the framework of the model of unipotential cell clone dynamics, assuming two alternative ways (scenarios) of an every new-born cell development, which in the long run define correspondingly the proliferating or differentiated cell status. The scenario choice is then supposed to be a random event influenced by both the inherent mitotic activity of the cell and the differentiation factors — special messengers synthesized by the differentiated cells. Differentiation factors being accepted by every-new born cell can change the way of cell development. Taking into account the clonal heterogeneity it was shown that such mechanism of the regulation of proliferation-differentiation processes can result in the selection of actively proliferating and insensitive with respect to differentiation factors action cells (that is to say, the cells with cancer phenotype). In the framework of investigation the cells with cancer phenotype (which is heritable within the variability of mother-daughter correlations)appears through the series of the permanent nonmutational changes in the proliferating cells by autoselection mechanism retaining for the division and generation of the progeny only that actively proliferating cells which are less sensitive with respect to the action of the differentiation factors. The progression of normal cell clone towards the appearance and increase of the number of the cells with cancer phenotype can be considered as a possible mechanism of carcinogenesis which is alternative to the clonal selection theory of cancer origin.