Modulation of Cell-Cell Adhesion by Integrin Signals in Oral Squamous Carcinoma Cells

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When cultured in the non-adherent dish coated with poly-HEMA, oral squamous carcinoma cells, MOK101, formed multicellular aggregates (MCA). In this process, the amount of E-cadherin in MCAs increased as MCAs became compact. Since the formation of MCAs was delayed by the existence of anti-E-cadherin inhibitory antibody, the cell-cell adhesion mediated by E-cadherin was important in the formation of MCAs. When MCAs were seeded on laminin 5 rich matrix and type I collagen, MCAs rearranged to monolayer colonies on both substrates. However, cell dissociation was observed only on laminin 5, but not on type I collagen. By western blotting analysis, the cell-scattering on laminin 5 was associated with the increase of β catenin in 0.2 % Triton X-100 soluble fraction, and tyrosine phosphorylation of β catenin was detected in scattering cells on laminin 5. Furthermore, antibodies against α3 and β1 integrin subunits blocked the cellscattering on laminin 5, while α2 and α6 integrin antibodies did not, suggesting that the in-out signal via α3β1 integrin was predominantly involved in this phenomenon. Finally, we tested if the activation of α3 or β1 integrin subunit could trigger the collapse of MCAs by cross-linking of these integrins on the surface of MCAs. A few microspikes, which was also observed during the rearrangement of MCAs on laminin 5, were formed on the surface of MCAs, although MCAs failed to be broken down.These results suggest that integrin signals are concerned in the modulation of cell-cell adhesion in oral squamous carcinoma cells. However, the involvement of growth factors and increased cellular motility in the dissociation of MCAs on laminin 5 remains to be clarified.