Matrix metalloproteinases and TGFβ1 modulate oral tumor cell matrix

• DOI: 10.1016/j.bbrc.2004.02.143
• Publication Date: 2004-03-06T10:39:24Z
• Authors: Dongmin Dang; Yongjian Yang; Xiaowu Li; Amha Atakilit; Joseph Regezi; David Eisele; Duncan Ellis; Daniel M. Ramos
• Keywords: Integrin beta Chains; Time Factors; Blotting, Western; Tenascin; Fibroblasts; Coculture Techniques; Matrix Metalloproteinases; Cell Line; Extracellular Matrix; Fibronectins; Enzyme Activation; 03 medical and health sciences; 0302 clinical medicine; Matrix Metalloproteinase 9; Transforming Growth Factor beta; Cell Line, Tumor; Culture Media, Conditioned; Carcinoma, Squamous Cell; Animals; Humans; Matrix Metalloproteinase 3; Mouth Neoplasms

The integrin beta6 has been shown to promote invasion and experimental metastasis by oral squamous cell carcinoma (SCC). In this study, we demonstrate that the expression of beta6 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 SCC9beta6 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 SCC9beta6/PTF cocultures were incubated with TGFbeta1, 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 TGFbeta1 are important for the modulation, composition, and maintenance of the ECM in oral SCC.