Matrix metalloproteinases and TGFbeta1 modulate oral tumor cell matrix.
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.
Dang
Dongmin
D
Department of Stomatology, University of California at San Francisco, San Francisco, CA 94143-0512, USA.
Yang
Yongjian
Y
Li
Xiaowu
X
Atakilit
Amha
A
Regezi
Joseph
J
Eisele
David
D
Ellis
Duncan
D
Ramos
Daniel M
DM
D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000502:physiology*; D009062:Mouth Neoplasms / Q000201:enzymology / Q000378:metabolism*; D019063:Tenascin / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1
D017077:Culture Media, Conditioned; D005353:Fibronectins; D039641:Integrin beta Chains; C508960:TGFB1 protein, human; D019063:Tenascin; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C072170:integrin beta6; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9