Vol. 107, No'. 2. 1982 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS July 30, 1982 Pages 663-669 GANGLIOSIDE GM1 SENSITIZES TUMOR CELLS TO GROWTH INHIBITORY GLYCOPEPTIDES Robert J. Kinders, David A. Rintoul and Terry C. Johnson Division of Biology Kansas State University, Manhattan, KS 66506 Retzeived June 18, 1982 We 'have purified and characterized a glycopeptide from surfaces of brain cortex cells that inhibits cellular protein synthesis in normal but not transformed cells. Data are presented that correlate the ability of C3H fibrosarcoma 1316 cells to avoid the inhibitor's activity with a re- duced cellular level of the ganglioside GMl. When 1316 cells were incubated with GM1 under conditions in which the ganglioside is incor- porated into the cells, the cells became sensitive to the inhibitor. Similar experiments with ceramide resulted in no change in 1316 sensitivity. In addition, when 1316 cells were incubated with GM1 for 18 h, they apparently metabolized GM1 to simpler gangliosides and lost their sen- sitivity to the glycopeptide inhibitor. INTRODUCTION -____ We have described the isolation, purification and characterization of glycopeptides, released from the surfaces of brain cortical cells by mild proteolysis, which are potent inhibitors of cell growth and protein synthesis (1,2). These glycopeptides may be naturally occurring growth regulators that mediate their effects by cell-cell contact in a manner similar to that proposed by Dulbecco and Stoker (3). These macromolecules irhibit protein synthesis in a reversible and non-lethal manner, at the level of elongation of nascent peptide chains, requiring membrane mediation ard/or an intra-cellular modification (4). The glycopeptides can inhibit pr,otein synthesis by 50% at a concentration of 2 x lo5 molecules per target cell, which is in the concentration range associated with hormone action (2). The inhibitor is most active against primary cells in culture, somewhat less active against established tissue culture cell lines, and relatively or completely ineffective against transformed or 663 0006-291X/82/140663-07$01.00/0 Copyright 0 1982 by Academic Press, Inc. All rights of reproduction in an-v form reserved.