This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aznavoorian, S. Articles by Engler, J. A. Search for Related Content PubMed PubMed Citation Articles by Aznavoorian, S. Articles by Engler, J. A.

Membrane Type I-Matrix Metalloproteinase-Mediated Degradation of Type I Collagen by Oral Squamous Cell Carcinoma Cells¹

Oral Cancer Research Center, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama, 35294-0005 [S. A., B. A. M., S. L. H., J. A. E.]; Department of Oral Biology, Indiana University, Indianapolis, Indiana, 46202 [L. J. W.]; and Research Genetics, Inc., Huntsville, Alabama 35801 [L. D. A-L.]

Oral squamous cell carcinomas are highly invasive lesions that destroy adjacent tissues and invade bone and muscle, which is most likely the result of matrix metalloproteinase (MMP) activity. We examined three cell lines derived from squamous cell carcinoma of the tongue for their intrinsic capacities to degrade interstitial collagen with the goal of identifying the matrix-degrading enzymes. SCC-25 and SCC-15 cells degrade reconstituted fibrillar type I collagen in the absence of exogenous growth factors or cytokines when seeded as a colony on dried films. Degradation is confined to the subjacent matrix, is enhanced 2–3-fold by phorbol ester, and is strictly MMP-dependent, as it is blocked by BB-94 and tissue inhibitor of metalloproteinases-2 but not by inhibitors of serine and cysteine proteinases. Both cell lines express active (M_r 57,000) membrane type I-MMP (MT1-MMP) on their surfaces, as detected by surface biotinylation and immunoprecipitation. Concomitantly, both cell lines activate endogenous MMP-2 when cultured on type I collagen films, as assessed by zymography. Phorbol ester treatment enhances collagen-induced MMP-2 activation, which is accompanied by the appearance of a surface-labeled M_r 43,000 form of MT1-MMP. Treatment of cells with a synthetic furin inhibitor, which inhibits processing of the MT1-MMP zymogen, blocks collagen degradation. In contrast, CAL 27 cells do not degrade collagen under either basal or phorbol 12-myristate 13-acetate-stimulated conditions. Although proMT1-MMP (M_r 63,000/65,000) is detectable in these cells by immunoblot analysis, they express greatly reduced levels of active MT1-MMP on their surfaces relative to SCC-25 and SCC-15 cells. Correspondingly, CAL 27 cells cultured on collagen express neither latent nor active gelatinases. Immunoblots of lysates and conditioned media revealed the constitutive expression of proMMP-1 and proMMP-13 in all three cell lines. We conclude that in the absence of exogenous growth factors or accessory stromal cells, degradation of interstitial collagen by oral squamous cell carcinoma cells requires a threshold level of active MT1-MMP on cell surfaces.

This article has been cited by other articles:

				K. Itatsu, M. Sasaki, J. Yamaguchi, S. Ohira, A. Ishikawa, H. Ikeda, Y. Sato, K. Harada, Y. Zen, H. Sato, et al. Cyclooxygenase-2 Is Involved in the Up-Regulation of Matrix Metalloproteinase-9 in Cholangiocarcinoma Induced by Tumor Necrosis Factor-{alpha} Am. J. Pathol., March 1, 2009; 174(3): 829 - 841. [Abstract] [Full Text] [PDF]

				J.-A. Cho, P. Osenkowski, H. Zhao, S. Kim, M. Toth, K. Cole, A. Aboukameel, A. Saliganan, L. Schuger, R. D. Bonfil, et al. The Inactive 44-kDa Processed Form of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Enhances Proteolytic Activity via Regulation of Endocytosis of Active MT1-MMP J. Biol. Chem., June 20, 2008; 283(25): 17391 - 17405. [Abstract] [Full Text] [PDF]

				H. Abdul-Hussien, R. G.V. Soekhoe, E. Weber, J. H. von der Thusen, R. Kleemann, A. Mulder, J. H. van Bockel, R. Hanemaaijer, and J. H.N. Lindeman Collagen Degradation in the Abdominal Aneurysm: A Conspiracy of Matrix Metalloproteinase and Cysteine Collagenases Am. J. Pathol., March 1, 2007; 170(3): 809 - 817. [Abstract] [Full Text] [PDF]

				P. Osenkowski, S. O. Meroueh, D. Pavel, S. Mobashery, and R. Fridman Mutational and Structural Analyses of the Hinge Region of Membrane Type 1-Matrix Metalloproteinase and Enzyme Processing J. Biol. Chem., July 15, 2005; 280(28): 26160 - 26168. [Abstract] [Full Text] [PDF]

				E. L. Rosenthal, W. Zhang, M. Talbert, K. P. Raisch, and G. E. Peters Extracellular Matrix Metalloprotease Inducer-Expressing Head and Neck Squamous Cell Carcinoma Cells Promote Fibroblast-Mediated Type I Collagen Degradation In vitro Mol. Cancer Res., April 1, 2005; 3(4): 195 - 202. [Abstract] [Full Text] [PDF]

				C. D. Andl, T. Mizushima, K. Oyama, M. Bowser, H. Nakagawa, and A. K. Rustgi EGFR-induced cell migration is mediated predominantly by the JAK-STAT pathway in primary esophageal keratinocytes Am J Physiol Gastrointest Liver Physiol, December 1, 2004; 287(6): G1227 - G1237. [Abstract] [Full Text] [PDF]

				J. H.N. Lindeman, R. Hanemaaijer, A. Mulder, P.D. S. Dijkstra, K. Szuhai, D. Bromme, J. H. Verheijen, and P. C.W. Hogendoorn Cathepsin K Is the Principal Protease in Giant Cell Tumor of Bone Am. J. Pathol., August 1, 2004; 165(2): 593 - 600. [Abstract] [Full Text] [PDF]

				H. Zhao, M. M. Bernardo, P. Osenkowski, A. Sohail, D. Pei, H. Nagase, M. Kashiwagi, P. D. Soloway, Y. A. DeClerck, and R. Fridman Differential Inhibition of Membrane Type 3 (MT3)-Matrix Metalloproteinase (MMP) and MT1-MMP by Tissue Inhibitor of Metalloproteinase (TIMP)-2 and TIMP-3 Regulates Pro-MMP-2 Activation J. Biol. Chem., March 5, 2004; 279(10): 8592 - 8601. [Abstract] [Full Text] [PDF]

				C. Guo and L. Piacentini Type I Collagen-induced MMP-2 Activation Coincides with Up-regulation of Membrane Type 1-Matrix Metalloproteinase and TIMP-2 in Cardiac Fibroblasts J. Biol. Chem., November 21, 2003; 278(47): 46699 - 46708. [Abstract] [Full Text] [PDF]

				H. G. Munshi, Y. I. Wu, E. V. Ariztia, and M. S. Stack Calcium Regulation of Matrix Metalloproteinase-mediated Migration in Oral Squamous Cell Carcinoma Cells J. Biol. Chem., October 25, 2002; 277(44): 41480 - 41488. [Abstract] [Full Text] [PDF]

				E. M. Tam, Y. I. Wu, G. S. Butler, M. S. Stack, and C. M. Overall Collagen Binding Properties of the Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) Hemopexin C Domain. THE ECTODOMAIN OF THE 44-kDa AUTOCATALYTIC PRODUCT OF MT1-MMP INHIBITS CELL INVASION BY DISRUPTING NATIVE TYPE I COLLAGEN CLEAVAGE J. Biol. Chem., October 4, 2002; 277(41): 39005 - 39014. [Abstract] [Full Text] [PDF]