Matrix metalloproteinases and TGFβ1 modulate oral tumor cell matrix

The integrin β6 has been shown to promote invasion and experimental metastasis by oral squamous cell carcinoma (SCC). In this study, we demonstrate that the expression of β6 by oral SCC9 cells increased activation of the UPA→MMP3→MMP9 pathway. We also demonstrate that the deposition of fibronectin and tenascin-C matrices by SCC9β6 cells and peritumor fibroblast cocultures is counter-regulated by the UPA→MMP3→MMP9 pathway. Suppression of individual components of this pathway increased the deposition of fibronectin, but decreased tenascin-C matrix assembly by the cocultures. When the SCC9β6/PTF cocultures were incubated with TGFβ1, the deposition of fibronectin and tenascin-C as well as the activation of MMP3 and MMP9 was increased. These results indicate that MMP3, MMP9, and TGFβ1 are important for the modulation, composition, and maintenance of the ECM in oral SCC.