Possible common mechanisms of morphological and growth-related alterations accompanying neoplastic transformation

Two main groups of phenotypic alterations usually accompany neoplastic transformations of cultured fibroblastic and epithelial cells: alterations of growth control and decreased formation of cell-substrate and cell-cell contacts. We suggest that both types of alterations are due to change of cell response to clustered membrane receptors. Clustering of certain receptors by corresponding ligands possibly induces a dual set of cellular reactions: (i) activation of cell proliferation preceded by an ordered sequence of prereplicative changes and (ii) attachment-clearing reactions that are associated with anchoring of ligand-receptor complexes by cytoskeletal components and may eventually lead to internalization of these complexes. The first stages of these two subsets of dual reactions are probably identical, but later the two chains of reactions are separated; completion of clearing reaction may stop further progress of the activation of proliferation. Attachment of the cell membrane to another surface can be regarded as a variant of unfinished clearing reaction. Transformed cells may be characterized by alterations of the dual reactions; the primary change may affect either the attachment-clearing branch or the common early stages preceding the separation of branches. These alterations may lead to facilitated activation of proliferation and also to primary or secondary decrease of the ability to perform attachment-clearing reactions in response to external ligands.