Density-dependent regulation of cell growth by contactinhibin and the contactinhibin receptor

Abstract

Homeostasis is the net result of a highly balanced network of growth-stimulating and growth-inhibitory signals. We have shown that density-dependent inhibition of growth in vitro is mediated by the interaction of contactinhibin with a 92 kD plasma membrane glycoprotein, CiR, the contactinhibin-binding capacity of which is regulated by phosphorylation.

p16INK4 mediates contact-inhibition of growth

“…Concomitantly, criss-crossed growth and the emergence of many foci, both being characteristic phenotypes of cultures of transformed cells, were observed. A twofold increase in cell density is the maximal value which can be achieved in con¯uent cultures of FH109 ®broblasts by impairing contactinhibition of growth, as shown in previous studies (Wieser et al, 1990;Gradl et al, 1995). Although we have not tested the hypothesis, according to the morphology of the cells in these cultures and in agreement with similar observations described in literature, it is suggested that in overcrowded cultures apoptosis takes place (Yasaka et al, 1996).…”

“…In FH109 cells, human embryonal diploid lung ®broblasts (Wieser et al, 1985), contactdependent inhibition of growth is exclusively mediated by the interaction of two cell membrane proteins on adjacent cells, i.e. by the glycoprotein, contactinhibin (Wieser et al, 1990), which binds to its receptor referred to as contactinhibin receptor (Gradl et al, 1995).Cell-cell contacts were imitated by the addition of glutaraldehyde-®xed cells (in which contactinhibin remains active, as its growth inhibitory activity is mediated exclusively by its N-glycans not a ected by the ®xation process) to sparsely seeded ®broblasts in the presence of serum. In previous studies we have demonstrated that this system mimics physiological conditions concerning cell proliferation and differentiation which occur in con¯uent cultures (Wieser et al, 1985;Wieser and Oesch, 1986), thus enabling the study of early e ects of cell-cell contact-dependent signals.…”

“…In FH109 cells, human embryonal diploid lung ®broblasts (Wieser et al, 1985), contactdependent inhibition of growth is exclusively mediated by the interaction of two cell membrane proteins on adjacent cells, i.e. by the glycoprotein, contactinhibin (Wieser et al, 1990), which binds to its receptor referred to as contactinhibin receptor (Gradl et al, 1995).…”

In vivo modulated N‐acyl side chain of N‐acetylneuraminic acid modulates the cell contact‐dependent inhibition of growth

“…Proliferation assays control and recognition system. It either acts as a specific These were performed according to Gradl et al [9]. Briefly, 5X103 recognition site, e.g.…”

“…We have shown previously that contact-deanti-rabbit antibodies (Sigma, Deisenhofen, Germany). Lectin-based pendent inhibition of the growth of non-transformed human detection of glycoprotein-bound sialic acids (all reagents from Boehringer Mannheim) was performed with digoxigenin-conjugated lectins fibroblasts is mediated by the plasma membrane glycoprotein followed by anti-digoxigenin antibodies according to the manufaccontactinhibin [8] and its receptor [9]. In addition, it has been turer's instructions.…”