Sulphate induces very fast cell rounding and detachment

Abstract

Within a few minutes of incubation with SO42-, cultured monolayer cells retract into round shapes with drastically reduced surface area. Concomitant elevation of phosphoinositide second messenger levels, viz, 1,2-diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), is observed. A causal relationship with sulphation seems to be suggested by finding (a) sulphation of an added acceptor, 4-methylumbelliferone, (b) sulphation of endogenous glycosaminoglycan (GAG) polymers, (c) inhibition by phenol sulphotransferase inhibitor, DCNP (2,6-dichloro-4-nitrophenol). DCNP also inhibits the second messenger production and cell rounding. Reduced surface area appears to be caused by massive plasma membrane internalization in a distinctive endocytosis which is also seen in cell rounding from directly imposed ionic gradients. Reducing the surface area would reduce the adhesive or attachment sites. Besides demonstrating a highly efficient cell detachment potential, huge macromolecules appear to be readily internalized. The association of sulphation, signal transduction and cell detachment is novel.