GROWTH-INHIBITION OF BALB C MOUSE KERATINOCYTES BY TGF-BETA-1 AND CERES-18 APPEARS TO ACT THROUGH DISTINCT MECHANISMS/

Cell growth is controlled by the complex interactions of both positive and negative growth modulators. Studies were performed to directly co mpare the growth inhibitors properties of TGF-beta 1 and CeReS-18, a n ovel cell surface sialoglycopeptide growth inhibitor, Growth inhibitio n by CeReS-18 and that by TGF-beta 1 shared some similarities although significant differences were apparent. Similarities included a dose-r esponsive inhibition of BALB/c mouse keratinocyte (MK) cell proliferat ion that could be nontoxic and reversible. Both CeReS-18 and TGF-beta 1 could equally inhibit the stimulation of DNA synthesis induced by se rum or keratinocyte growth factor in MK cells, and in both cases the i nhibition was not due to decreased KGF binding to the target cell surf ace receptor. Inhibition of cell proliferation with CeReS-18, followed by an immediate reincubation with either CeReS-18 or TGF-beta 1, sugg ested that the sites of arrest mediated by both inhibitors were simila r but not necessarily identical, However, recovery from CeReS-18-induc ed growth inhibition could be achieved by either removing the CeReS-18 or adding calcium directly to CeReS-18-inhibited MK cells, while reco very from TGF-beta 1-induced growth arrest could be reversed only by T GF-beta 1 removal. In addition, the sensitivity of MK cells to CeReS-1 8-induced cell cycle arrest could be altered by changing the extracell ular calcium concentration, but sensitivity to TGF-beta 1 was unaffect ed by the calcium environment of the MK cells. While recovery from cel l cycle arrest was rapid and complete with MK cell cultures inhibited with CeReS-18, removal of TGF-beta 1 led to a slower and incomplete re covery of cell cycling. (C) 1996 Academic Press, Inc.