Growth control of human foreskin fibroblasts and inhibition of extracellular sialidase activity by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid.

Normal human fibroblasts have two extreme modes of existence in culture, quiescent and proliferative. The growth and division of these cells are usually well regulated by the action of various endogenously generated stimulators and inhibitors. We have speculated that an extracellular sialidase may be involved in the regulation of growth and that inhibition of this activity might decrease or abolish cell growth. To test this hypothesis, we have incubated preconfluent cultures of fibroblasts in the presence and absence of a potent sialidase inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Treatment of cells with this inhibitor resulted in the inhibition of an extracellular sialidase activity for up to 24 h and had a marked growth inhibitory effect in a concentration-dependent manner. The effect of the inhibitor on cell proliferation was specific and reversible. During a chase period of 48 h after pulse labeling cells with [3H]N-acetylmannosamine and [14C]serine, there was a 15% decrease of [3H]sialic acid in the membrane-bound GM3 with 80 microM inhibitor in the medium, as compared with a 32% decrease in the controls. Our results suggest that an extracellular sialidase may participate in cell-surface modifications that accompany (or control) the changes observed when cells traverse the cell cycle, from the quiescent to the proliferative phase.