Epithelial cell motility: the effect of 2-deoxyglucose on cell migration, ATP production, and the structure of the cytoplasmic ground substance in lamellipodia of epithelial cells in culture.

Abstract

Using a line of epithelial cells (SCCA5) derived from a spontaneous rat carcinoma, the glucose analogue 2-deoxyglucose (2DG) has been shown by time-lapse cinemicrography to produce a cessation of motility by 1 hour that can be reversed by replacement of the 2DG, and does not occur in equivalent media with or without glucose or in 2DG-containing media with added pyruvate and citrate. The effect on the cells at the edge of an epithelial island is to prevent the formation of new lamellipodia and produce a progressive retraction and condensation of lamellipodia already present. This effect of 2DG on motility corresponds with a significant reduction in the level of ATP that is partially restored after 30 minutes in the recovery incubation. Only a slight reduction in protein synthesis occurs in the presence of 2DG. The external morphology and the cytoplasmic ground substance of the cells were studied by scanning electron microscopy and high voltage electron microscopy respectively. It was found that after incubation in 2DG for 1 hour the outline of the free edges of the cells was distorted resulting in redistribution of microvilli, condensation of cytoplasm into strands, and irregular projections from the edges of residual lamellipodia. The structure of the cytoplasmic ground substance in lamellipodia from cells incubated in 2DG for 3 hours was distinctly different from that in cells incubated for 3 hours in 2DG then recovered for 25 minutes, or in cells incubated in glucose-containing medium for 3 hours. In the 2DG-treated cells the lattice-like structure evident in critical-point-dried cells was condensed into short thick strands that terminated in bulbous ends, whereas in cells recovered for 25 minutes the lattice material was elongated and tapering and the interlattice space relatively expanded. The results obtained support the concept of modulation occurring in the structure of the microtrabecular lattice component of the cytoplasmic ground substance coincident with alterations in cell function and metabolic state.