Abstract
The growth control of non-transformed mammalian cells is under the stringent control of the actual cell density. With increasing cell densities, proliferation progressively decreases and eventually ceases at confluency. We have isolated a plasma membrane glycoprotein, referred to as contactinhibin, which is responsible for the contact-dependent inhibition of growth of human diploid fibroblast. It inhbits the proliferation of sparsely seeded cells in a reversible, non-toxic manner in immobilised form at pmolar concentrations, while in soluble form it is inactive. The biologically active moiety resides exclusively within the N-glycosidically linked glycans. In addition, for an efficient inhibition of growth, terminal β-glycosidically linked galactose residues have to be present on the N-glycans. By culturing human fibroblasts in the presence of anti-contactinhibin-antibodies the cells grow to 2 fold higher saturation density, together with an extentive criss-cross and focal growth pattern. Contactinhibin, interacts specifically with a plasma membrane receptor, whose binding activity is inversely regulated by the extent of phosphorylation. Cancer growth is suggested to arise from an overphosphorylation of the contactinhibin-receptor.
