Aproliferin: a modulator of proliferative potential

Abstract

Cellular differentiation proceeds through a series of steps in which cells undergo modifications in cellular phenotype and proliferative potential. Differentiation has been extensively studied in 3T3-T mesenchymal stem cells and growth arrest, non-terminal and terminal differentiation have been identified as three distinct stages in the adipocyte differentiation of these cells. The terminal stage of differentiation is associated with irreversible loss of proliferative potential and commitment to the expression of the adipocyte phenotype. A protein has been partially purified from human plasma that can induce the transition of 3T3-T adipocytes from the non-terminal to the terminal state of differentiation. This protein, designated aproliferin, has a mol. wt of approximately 45,000 and is trypsin, acid and heat labile. Induction of terminal differentiation by aproliferin is associated with changes in the synthesis of a limited number of cellular proteins. The ability of aproliferin to induce terminal differentiation in non-terminally differentiated cells is highly specific as a wide variety of pharmacological and biochemical agents do not mimic the effects of this agent. Apoliferin may be one of an emerging class of molecules which can affect differentiation and induce irreversible changes in cell function.