Difference in Topology of Normal and Tumour Cell Membranes shown by Different Surface Distributions of Ferritin-conjugated Concanavalin A

Abstract

THE observations of Burger and Goldberg¹ on the differential agglutinability of malignant cells by the saccharide-binding protein, wheat germ agglutinin (WGA), have prompted other investigators to study the nature of tumour cell surfaces using similar reagents. A variety of other plant agglutinins specifically agglutinate certain oncogenic virus-transformed cells at much lower concentrations than those required to agglutinate their normal parental lines. In addition to WGA^1,2 (specific for binding N-acetyl-D-glucosamine-like residues¹), these include concanavalin A (Con A)^3,4 (specific for binding α-D-glucose or α-D-mannose-like residues⁵), soy bean agglutinin (SBA)^6,7 (specific for binding N-acetyl-D-galactosamine and D-galactose-like residues⁶), and Ricinus communis agglutinin (specific for binding D-galactose and L-arabinose-like residues) (G. L. N. and J. Blaustein, in preparation). To explain this differential agglutinability phenomenon, Burger² proposed that the agglutinin-binding sites on normal cells could have undergone three possible types of change after transformation: (a) the normal parent cell may have no agglutinin sites, and after transformation a complete de novo synthesis of agglutinin sites occurs; (b) the normal parent cell may have agglutinin sites, but not enough for agglutination, and transformation results in an increase in the number of agglutinin sites; or (c) the normal parent cell agglutinin sites remain constant in number after transformation; but this process results in an exposure of “cryptic” agglutinin sites and the transformed cell is rendered agglutinable. Several workers^8,10,19 postulate a fourth type of change: (d) the normal parent cell agglutinin sites remain constant in number after transformation but the topological distribution of agglutinin sites changes to a distribution more favourable for agglutination. The first and second mechanisms have proved to be unlikely as originally suggested², because agglutinin surface receptors are present on normal cells², and they are present in the same amounts on normal or transformed cells. This latter finding has been demonstrated in saturation binding experiments using purified ¹²⁵I-labelled WGA⁸, Con A^8,9 and SBA¹⁰, with results contrary to earlier reports using ⁶³Ni-labelled Con A³.