Cytomatrix reorganization in dimethyl sulfoxide-induced "Qi" substate murine hepatic tumor cells

Cultured murine hepatic tumor (HT) cells respond to the polar solvent dimethylsulfoxide (DMSO) with specific alterations in morphology, proliferative kinetics, and biochemical properties. These include entrance into a quiescent "Qi" substate (characterized by accumulation of cells in G1 phase and lowered cellular RNA content), enhanced production of liver-specific proteins, and decreased expression of growth traits characteristic of the transformed phenotype. Entrance of HT cells into Qi was associated with increased monolayer compaction and a shift from an elaborate surface fibronectin (FN) network to a sparse and restricted distribution of FN fibers. This marked decrease in the extent and complexity of the cellular FN network, as a consequence of DMSO exposure, was reflected in a 90% decline in the amount of FN secreted into the culture medium. These data complement previous studies indicating that the accumulation and composition of liver cell matrix substances reflect altered patterns of hepatocyte-specific gene expression. In the HT cell system, DMSO appears to act in a bifunctional manner, increasing the production of certain tissue-specific proteins (e.g., albumin and alpha-fetoprotein) while decreasing the secretion and deposition of other cellular components (FN). DMSO may directly regulate expression of these proteins in HT cells or alter the pattern of cellular response to specific autocrine growth factors.