Contact inhibition of cell spreading: a mechanism for the maintenance of thyroid cell aggregation in vitro.
When freshly isolated porcine thyroid cells are stimulated with thyrotropin (TSH) they organize to form functional follicles in conventional substrate-adherent culture. Cell aggregation is essential for follicular reorganization and is likely to be influenced by the balance between cell-cell adhesion (promoting aggregation) and cell-substrate adhesion (favoring spreading and monolayer formation). Recently we observed that TSH potentiated cell-cell adhesion and in the present study we have sought evidence that TSH might also regulate cell-substrate adhesion. Two parameters of cell-substrate adhesion, namely, cell attachment to collagen and cell spreading upon collagen, were measured using preparations of isolated single cells and of multicellular aggregates. TSH had no effect upon the attachment or spreading of single cells, but inhibited aggregate spreading without affecting aggregate attachment. The possibility that cell-cell contact modulated the response to TSH in aggregates, but not in single cells, was confirmed using a cell-free membrane preparation which inhibited the spreading of single cells but not their rate of attachment. Moreover, TSH potentiated the inhibitory effect of membranes on the spreading of single cells. Heparin also specifically inhibited the spreading of both single cells and cell aggregates, suggesting that a heparin-sensitive adhesive mechanism might be recruited as thyroid cells spread. We conclude that thyroid cell-substrate adhesion is regulated by a synergistic interaction between cell-cell contact and TSH which preferentially inhibited cell spreading but not attachment. Such contact-dependent inhibition of cell spreading is predicted to preserve cell aggregates and hence contribute to the maintenance of thyroid follicular differentiation in vitro.