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Science 11 July 1997:
Vol. 277. no. 5323, pp. 225 - 228
DOI: 10.1126/science.277.5323.225
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Reports

Induction of Cell Migration by Matrix Metalloprotease-2 Cleavage of Laminin-5

Gianluigi Giannelli, Jutta Falk-Marzillier, Oronzo Schiraldi, William G. Stetler-Stevenson, Vito Quaranta *

Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and tumor invasion. Specific cleavage of laminin-5 (Ln-5) by matrix metalloprotease-2 (MMP2) was shown to induce migration of breast epithelial cells. MMP2 cleaved the Ln-5 gamma 2 subunit at residue 587, exposing a putative cryptic promigratory site on Ln-5 that triggers cell motility. This altered form of Ln-5 is found in tumors and in tissues undergoing remodeling, but not in quiescent tissues. Cleavage of Ln-5 by MMP2 and the resulting activation of the Ln-5 cryptic site may provide new targets for modulation of tumor cell invasion and tissue remodeling.

G. Giannelli, Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA, and Institute of Clinica Medica II, Università degli Studi Bari, 70124 Bari, Italy.
J. Falk-Marzillier and V. Quaranta, Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
O. Schiraldi, Institute of Clinica Medica II, Università degli Studi Bari, 70124 Bari, Italy.
W. G. Stetler-Stevenson, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
*   To whom correspondence should be addressed. E-mail: quaranta{at}scripps.edu

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Sci. STKE 2003, pe24
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Gelatinase A (MMP-2) Is Necessary and Sufficient for Renal Tubular Cell Epithelial-Mesenchymal Transformation.
S. Cheng and D. H. Lovett (2003)
Am. J. Pathol. 162, 1937-1949
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Selective Hydrolysis of Triple-helical Substrates by Matrix Metalloproteinase-2 and -9.
J. L. Lauer-Fields, T. Sritharan, M. S. Stack, H. Nagase, and G. B. Fields (2003)
J. Biol. Chem. 278, 18140-18145
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Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases: Structure, Function, and Biochemistry.
R. Visse and H. Nagase (2003)
Circ. Res. 92, 827-839
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A Residue in the S2 Subsite Controls Substrate Selectivity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9.
E. I. Chen, W. Li, A. Godzik, E. W. Howard, and J. W. Smith (2003)
J. Biol. Chem. 278, 17158-17163
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Membrane Type-1-Matrix Metalloproteinase Expressed by Prostate Carcinoma Cells Cleaves Human Laminin-5 {beta}3 Chain and Induces Cell Migration.
T. S. Udayakumar, M. L. Chen, E. L. Bair, D. C. von Bredow, A. E. Cress, R. B. Nagle, and G. T. Bowden (2003)
Cancer Res. 63, 2292-2299
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Mammalian Tolloid Metalloproteinase, and Not Matrix Metalloprotease 2 or Membrane Type 1 Metalloprotease, Processes Laminin-5 in Keratinocytes and Skin.
D. P. Veitch, P. Nokelainen, K. A. McGowan, T.-T. Nguyen, N. E. Nguyen, R. Stephenson, W. N. Pappano, D. R. Keene, S. M. Spong, D. S. Greenspan, et al. (2003)
J. Biol. Chem. 278, 15661-15668
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Binding to EGF receptor of a laminin-5 EGF-like fragment liberated during MMP-dependent mammary gland involution.
S. Schenk, E. Hintermann, M. Bilban, N. Koshikawa, C. Hojilla, R. Khokha, and V. Quaranta (2003)
J. Cell Biol. 161, 197-209
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Extracellular Cleavage of Bullous Pemphigoid Antigen 180/Type XVII Collagen and Its Involvement in Hemidesmosomal Disassembly.
Y. Hirako, K. Yoshino, D. Zillikens, and K. Owaribe (2003)
J. Biochem. 133, 197-206
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Laminin {gamma}2-Chain Fragment in the Circulation: A Prognostic Indicator of Epithelial Tumor Invasion.
M. Katayama, N. Sanzen, A. Funakoshi, and K. Sekiguchi (2003)
Cancer Res. 63, 222-229
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Laminin-6 Is Activated by Proteolytic Processing and Regulates Cellular Adhesion and Migration Differently from Laminin-5.
T. Hirosaki, Y. Tsubota, Y. Kariya, K. Moriyama, H. Mizushima, and K. Miyazaki (2002)
J. Biol. Chem. 277, 49287-49295
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Sustained Expression of Homeobox D10 Inhibits Angiogenesis.
C. Myers, A. Charboneau, I. Cheung, D. Hanks, and N. Boudreau (2002)
Am. J. Pathol. 161, 2099-2109
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Deficiency in Matrix Metalloproteinase Gelatinase B (MMP-9) Protects against Retinal Ganglion Cell Death after Optic Nerve Ligation.
S. K. Chintala, X. Zhang, J. S. Austin, and M. E. Fini (2002)
J. Biol. Chem. 277, 47461-47468
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EGF controls the in vivo developmental potential of a mammary epithelial cell line possessing progenitor properties.
M.-A. Deugnier, M. M. Faraldo, B. Janji, P. Rousselle, J. P. Thiery, and M. A. Glukhova (2002)
J. Cell Biol. 159, 453-463
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Induction of a laminin isoform and alpha 3beta 1-integrin in renal ischemic injury and repair in vivo.
A. Zuk and K. S. Matlin (2002)
Am J Physiol Renal Physiol 283, F971-F984
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Dynamics of the alpha 6beta 4 Integrin in Keratinocytes.
C. A. W. Geuijen and A. Sonnenberg (2002)
Mol. Biol. Cell 13, 3845-3858
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Calcium Regulation of Matrix Metalloproteinase-mediated Migration in Oral Squamous Cell Carcinoma Cells.
H. G. Munshi, Y. I. Wu, E. V. Ariztia, and M. S. Stack (2002)
J. Biol. Chem. 277, 41480-41488
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Matrix Metalloproteinase-9-Dependent Exposure of a Cryptic Migratory Control Site in Collagen is Required before Retinal Angiogenesis.
M. Hangai, N. Kitaya, J. Xu, C. K. Chan, J. J. Kim, Z. Werb, S. J. Ryan, and P. C. Brooks (2002)
Am. J. Pathol. 161, 1429-1437
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Fibronectin Polymerization Regulates the Composition and Stability of Extracellular Matrix Fibrils and Cell-Matrix Adhesions.
J. Sottile and D. C. Hocking (2002)
Mol. Biol. Cell 13, 3546-3559
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Identification of Biologically Active Sequences in the Laminin alpha 4 Chain G Domain.
I. Okazaki, N. Suzuki, N. Nishi, A. Utani, H. Matsuura, H. Shinkai, H. Yamashita, Y. Kitagawa, and M. Nomizu (2002)
J. Biol. Chem. 277, 37070-37078
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Hyaluronan-CD44 interaction hampers migration of osteoclast-like cells by down-regulating MMP-9.
P. Spessotto, F. M. Rossi, M. Degan, R. Di Francia, R. Perris, A. Colombatti, and V. Gattei (2002)
J. Cell Biol. 158, 1133-1144
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Metalloproteases and Guidance of Retinal Axons in the Developing Visual System.
C. A. Webber, J. C. Hocking, V. W. Yong, C. L. Stange, and S. McFarlane (2002)
J. Neurosci. 22, 8091-8100
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The Role of ADAM 15 in Glomerular Mesangial Cell Migration.
J. Martin, L. V. Eynstone, M. Davies, J. D. Williams, and R. Steadman (2002)
J. Biol. Chem. 277, 33683-33689
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