Activation of an alpha-fetoprotein/receptor pathway in human normal and malignant peripheral blood mononuclear cells

Alpha-fetoprotein (AFP) is mainly synthesized by the fetal liver and the yolk sac with minor contributions of several non-hepatic fetal tissues, variable according to the species considered. Most fetal cells, whatever their origin, possess the ability to bind and to endocytose the protein. This property, which is considered to be lost in differentiated cells of the adult, may be resumed in tumoral cells and is due to the expression of specific AFP receptors at the cell surface. Cytochemical and immunological approaches, combined with in situ hybridization, were used to investigate the specific uptake and synthesis of human AFP in several classes of peripheral blood mononuclear cells (PBMC) and in several malignant cell lines of hematopoietic origin. With the exception of quiescent T lymphocytes, all cells investigated specifically bound AFP. Both normal and malignant blood mononuclear cells expressed mRNA transcripts of AFP which were translated into the protein during a well established period of cellular growth. These results suggest that an AFP/receptor autocrine system might operate in normal and malignant blood mononuclear cells. Its physiological role is discussed in relation to recent work from our laboratory--providing experimental evidence that AFP, throughout its interaction with specific cell receptors, regulates and facilitates the entry of fatty acids into living cells undergoing growth and differentiation.