MITOGENIC EFFECTS OF A MESOTHELIAL CELL-GROWTH FACTOR - EVIDENCE FOR A POTENTIAL AUTOCRINE REGULATION OF NORMAL AND MALIGNANT MESOTHELIAL CELL-PROLIFERATION

We have investigated the growth-factor-like activity of a approximatel y 200-kDa, IP 8.3, cytoplasmic glycoprotein, the expression of which a ppears to be restricted to normal and malignant human mesothelium. Thi s substance stimulated the growth of human mesothelioma cell cultures at greater rates than did foetal calf serum, but it failed to induce p roliferation of lung carcinoma cell cultures. In addition, we have tri ed to trace the biosynthetic pathway of this mitogenic factor in norma l human mesothelial cells by means of immuno-electron microscopy with a polyclonal antibody directed against this molecule. Positive immunog old labelling was found in the lumina of the cisternae of the endoplas mic reticulum, to a lesser extent on the outer surface of the plasma m embrane, and also in structures corresponding to the coated pits. Thes e ultrastructural findings are consistent with the hypothesis of the g lycosylation of the newly synthesized protein in the endoplasmic retic ulum and the subsequent uptake of the secreted molecule, which accumul ates in the coated pits before internalization. The results suggest th at this mitogenic glycoprotein could play a role in an autocrine growt h control mechanism influencing mesothelial cell proliferation.