| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Department of Molecular Immunology and
Pathology*
and the Department of Virology and
Oncology,¶
Cancer Research Institute, and the
Department of Neurosurgery,
School of
Medicine, Kanazawa University, Kanazawa, the Department of
Pathology,
School of Medicine, Keio
University, Tokyo, the Biopharmaceutical
Department,§
Fuji Chemical Industries, Ltd.,
Takaoka, and Department of Cancer Cell Research,||
Institute of Medical Science, University of Tokyo, Tokyo, Japan
Three different membrane-type matrix metalloproteinases (MT1-, MT2-, and MT3-MMPs) are known to activate in vitro the zymogen of MMP-2 (pro-MMP-2, progelatinase A), which is one of the key MMPs in invasion and metastasis of various cancers. In the present study, we have examined production and activation of pro-MMP-2, expression of MT1-, MT2-, and MT3-MMPs and their correlation with pro-MMP-2 activation, and localization of MMP-2, MT1-MMP, and MT2-MMP in human astrocytic tumors. The sandwich enzyme immunoassay demonstrates that the production levels of pro-MMP-2 in the anaplastic astrocytomas and glioblastomas are significantly higher than that in the low-grade astrocytomas (P < 0.05 and P < 0.01, respectively), metastatic brain tumors (P < 0.05), or normal brains (P < 0.01). Gelatin zymography indicates that the pro-MMP-2 activation ratio is significantly higher in the glioblastomas than in other astrocytic tumors (P < 0.01), metastatic brain tumors (P < 0.01), and normal brains (P < 0.01). The quantitative reverse transcription polymerase chain reaction analyses demonstrate that MT1-MMP and MT2-MMP are expressed predominantly in glioblastoma tissues (17/17 and 12/17 cases, respectively), and their expression levels increase significantly as tumor grade increases. MT3-MMP is detectable in both astrocytic tumor and normal brain tissues, but the mean expression level is approximately 50-fold lower compared with that of MT1-MMP and MT2-MMP in the glioblastomas. The activation ratio of pro-MMP-2 correlates directly with the expression levels of MT1-MMP and MT2-MMP but not MT3-MMP. In situ hybridization indicates that neoplastic astrocytes express MT1-MMP and MT2-MMP in the glioblastoma tissues (5/5 cases and 5/5 cases, respectively). Immunohistochemically, MT1-MMP and MT2-MMP are localized to the neoplastic astrocytes in glioblastoma samples (17/17 cases and 12/17 cases, respectively), which are also positive for MMP-2. In situ zymography shows gelatinolytic activity in the glioblastoma tissues but not in the normal brain tissues. These results suggest that both MT1-MMP and MT2-MMP play a key role in the activation of pro-MMP-2 in the human malignant astrocytic tumors and that the gelatinolytic activity is involved in the astrocytic tumor invasion.
This article has been cited by other articles:
 |
|
 |
|
  C. Nyalendo, E. Beaulieu, H. Sartelet, M. Michaud, N. Fontaine, D. Gingras, and R. Beliveau Impaired tyrosine phosphorylation of membrane type 1-matrix metalloproteinase reduces tumor cell proliferation in three-dimensional matrices and abrogates tumor growth in mice Carcinogenesis, August 1, 2008; 29(8): 1655 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Smith, D. Zurakowski, A. Saad, R. M. Scott, and M. A. Moses Urinary Biomarkers Predict Brain Tumor Presence and Response to Therapy Clin. Cancer Res., April 15, 2008; 14(8): 2378 - 2386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Hodgkinson, G. Duncan, L. Wang, C. J. Pennington, D. R. Edwards, and I. M. Wormstone MMP and TIMP Expression in Quiescent, Dividing, and Differentiating Human Lens Cells Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4192 - 4199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Nyalendo, M. Michaud, E. Beaulieu, C. Roghi, G. Murphy, D. Gingras, and R. Beliveau Src-dependent Phosphorylation of Membrane Type I Matrix Metalloproteinase on Cytoplasmic Tyrosine 573: ROLE IN ENDOTHELIAL AND TUMOR CELL MIGRATION J. Biol. Chem., May 25, 2007; 282(21): 15690 - 15699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Mayes, Y. Hu, Y. Teng, E. Siegel, X. Wu, K. Panda, F. Tan, W.K. A. Yung, and Y.-H. Zhou PAX6 Suppresses the Invasiveness of Glioblastoma Cells and the Expression of the Matrix Metalloproteinase-2 Gene. Cancer Res., October 15, 2006; 66(20): 9809 - 9817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Morrison and C. M. Overall TIMP Independence of Matrix Metalloproteinase (MMP)-2 Activation by Membrane Type 2 (MT2)-MMP Is Determined by Contributions of Both the MT2-MMP Catalytic and Hemopexin C Domains J. Biol. Chem., September 8, 2006; 281(36): 26528 - 26539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, S. Sarkar, and V.W. Yong The chemokine stromal cell derived factor-1 (CXCL12) promotes glioma invasiveness through MT2-matrix metalloproteinase Carcinogenesis, December 1, 2005; 26(12): 2069 - 2077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L.M. Lamfers, D. Gianni, C.-H. Tung, S. Idema, F. H.E. Schagen, J. E. Carette, P. H.A. Quax, V. W. Van Beusechem, W. P. Vandertop, C. M.F. Dirven, et al. Tissue Inhibitor of Metalloproteinase-3 Expression from an Oncolytic Adenovirus Inhibits Matrix Metalloproteinase Activity In vivo without Affecting Antitumor Efficacy in Malignant Glioma Cancer Res., October 15, 2005; 65(20): 9398 - 9405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Abraham, J. Schafer, M. Rothe, J. Bange, P. Knyazev, and A. Ullrich Identification of MMP-15 as an Anti-apoptotic Factor in Cancer Cells J. Biol. Chem., October 7, 2005; 280(40): 34123 - 34132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Noda, S. Ishida, H. Shinoda, T. Koto, T. Aoki, K. Tsubota, Y. Oguchi, Y. Okada, and E. Ikeda Hypoxia Induces the Expression of Membrane-Type 1 Matrix Metalloproteinase in Retinal Glial Cells Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3817 - 3824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Nemori, M. Yamamoto, F. Kataoka, G. Hashimoto, H. Arakatsu, T. Shiomi, and Y. Okada Development of In Situ Zymography to Localize Active Matrix Metalloproteinase-7 (Matrilysin-1) J. Histochem. Cytochem., October 1, 2005; 53(10): 1227 - 1234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhai, K. B. Hotary, B. Nan, F. X. Bosch, N. Munoz, S. J. Weiss, and K. R. Cho Expression of Membrane Type 1 Matrix Metalloproteinase Is Associated with Cervical Carcinoma Progression and Invasion Cancer Res., August 1, 2005; 65(15): 6543 - 6550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Kaufman, C. P. Brangwynne, K. E. Kasza, E. Filippidi, V. D. Gordon, T. S. Deisboeck, and D. A. Weitz Glioma Expansion in Collagen I Matrices: Analyzing Collagen Concentration-Dependent Growth and Motility Patterns Biophys. J., July 1, 2005; 89(1): 635 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kodama, E. Ikeda, A. Okada, T. Ohtsuka, M. Shimoda, T. Shiomi, K. Yoshida, M. Nakada, E. Ohuchi, and Y. Okada ADAM12 Is Selectively Overexpressed in Human Glioblastomas and Is Associated with Glioblastoma Cell Proliferation and Shedding of Heparin-Binding Epidermal Growth Factor Am. J. Pathol., November 1, 2004; 165(5): 1743 - 1753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kaikita, T. Hayasaki, T. Okuma, W. A. Kuziel, H. Ogawa, and M. Takeya Targeted Deletion of CC Chemokine Receptor 2 Attenuates Left Ventricular Remodeling after Experimental Myocardial Infarction Am. J. Pathol., August 1, 2004; 165(2): 439 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Ozen, B. Krebs, B. Hemmerlein, A. Pekrun, H. Kretzschmar, and J. Herms Expression of Matrix Metalloproteinases and Their Inhibitors in Medulloblastomas and Their Prognostic Relevance Clin. Cancer Res., July 15, 2004; 10(14): 4746 - 4753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Frederiks and O. R.F. Mook Metabolic Mapping of Proteinase Activity with Emphasis on In Situ Zymography of Gelatinases: Review and Protocols J. Histochem. Cytochem., June 1, 2004; 52(6): 711 - 722. [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]
|
|
|
|
|
|
G. Velasco-Loyden, J. Arribas, and F. Lopez-Casillas The Shedding of Betaglycan Is Regulated by Pervanadate and Mediated by Membrane Type Matrix Metalloprotease-1 J. Biol. Chem., February 27, 2004; 279(9): 7721 - 7733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Hosokawa, K. Nonaka, M. Morifuji, L. Shum, and M. Ohishi TGF-{beta}3 Decreases Type I Collagen and Scarring after Labioplasty J. Dent. Res., July 1, 2003; 82(7): 558 - 564. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nakada, H. Miyamori, J. Yamashita, and H. Sato Testican 2 Abrogates Inhibition of Membrane-type Matrix Metalloproteinases by Other Testican Family Proteins Cancer Res., June 15, 2003; 63(12): 3364 - 3369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Le, A. Besson, D. K. Fogg, K.-S. Choi, D. M. Waisman, C. G. Goodyer, B. Rewcastle, and V. W. Yong Exploitation of Astrocytes by Glioma Cells to Facilitate Invasiveness: A Mechanism Involving Matrix Metalloproteinase-2 and the Urokinase-Type Plasminogen Activator-Plasmin Cascade J. Neurosci., May 15, 2003; 23(10): 4034 - 4043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Noda, S. Ishida, M. Inoue, K.-i. Obata, Y. Oguchi, Y. Okada, and E. Ikeda Production and Activation of Matrix Metalloproteinase-2 in Proliferative Diabetic Retinopathy Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 2163 - 2170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Nuttall, C. J. Pennington, J. Taplin, A. Wheal, V. W. Yong, P. A. Forsyth, and D. R. Edwards Elevated Membrane-Type Matrix Metalloproteinases in Gliomas Revealed by Profiling Proteases and Inhibitors in Human Cancer Cells Mol. Cancer Res., March 1, 2003; 1(5): 333 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Enomoto, I. Inoki, K. Komiya, T. Shiomi, E. Ikeda, K.-i. Obata, H. Matsumoto, Y. Toyama, and Y. Okada Vascular Endothelial Growth Factor Isoforms and Their Receptors Are Expressed in Human Osteoarthritic Cartilage Am. J. Pathol., January 1, 2003; 162(1): 171 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Choe, J. K. Park, L. Jouben-Steele, T. J. Kremen, L. M. Liau, H. V. Vinters, T. F. Cloughesy, and P. S. Mischel Active Matrix Metalloproteinase 9 Expression Is Associated with Primary Glioblastoma Subtype Clin. Cancer Res., September 1, 2002; 8(9): 2894 - 2901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Limb, J. T. Daniels, R. Pleass, D. G. Charteris, P. J. Luthert, and P. T. Khaw Differential Expression of Matrix Metalloproteinases 2 and 9 by Glial Muller Cells : Response to Soluble and Extracellular Matrix-Bound Tumor Necrosis Factor-{alpha} Am. J. Pathol., May 1, 2002; 160(5): 1847 - 1855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Mahloogi, D. E. Bassi, and A. J.P. Klein-Szanto Malignant conversion of non-tumorigenic murine skin keratinocytes overexpressing PACE4 Carcinogenesis, April 1, 2002; 23(4): 565 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wang and E. G. Lakatta Altered Regulation of Matrix Metalloproteinase-2 in Aortic Remodeling During Aging Hypertension, April 1, 2002; 39(4): 865 - 873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kang, H. Nagase, and D. Pei Activation of Membrane-type Matrix Metalloproteinase 3 Zymogen by the Proprotein Convertase Furin in the trans-Golgi Network Cancer Res., February 1, 2002; 62(3): 675 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Hotary, I. Yana, F. Sabeh, X.-Y. Li, K. Holmbeck, H. Birkedal-Hansen, E. D. Allen, N. Hiraoka, and S. J. Weiss Matrix Metalloproteinases (MMPs) Regulate Fibrin-invasive Activity via MT1-MMP-dependent and -independent Processes J. Exp. Med., January 28, 2002; 195(3): 295 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Deryugina, L. Soroceanu, and A. Y. Strongin Up-Regulation of Vascular Endothelial Growth Factor by Membrane-type 1 Matrix Metalloproteinase Stimulates Human Glioma Xenograft Growth and Angiogenesis Cancer Res., January 1, 2002; 62(2): 580 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Morrison, G. S. Butler, H. F. Bigg, C. R. Roberts, P. D. Soloway, and C. M. Overall Cellular Activation of MMP-2 (Gelatinase A) by MT2-MMP Occurs via a TIMP-2-independent Pathway J. Biol. Chem., December 7, 2001; 276(50): 47402 - 47410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nakada, A. Yamada, T. Takino, H. Miyamori, T. Takahashi, J. Yamashita, and H. Sato Suppression of Membrane-type 1 Matrix Metalloproteinase (MMP)-mediated MMP-2 Activation and Tumor Invasion by Testican 3 and Its Splicing Variant Gene Product, N-Tes Cancer Res., December 1, 2001; 61(24): 8896 - 8902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kita, T. Takino, M. Nakada, T. Takahashi, J. Yamashita, and H. Sato Expression of Dominant-negative Form of Ets-1 Suppresses Fibronectin-stimulated Cell Adhesion and Migration Through Down-Regulation of Integrin {alpha}5 Expression in U251 Glioma Cell Line Cancer Res., November 1, 2001; 61(21): 7985 - 7991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Maher, F. B. Furnari, R. M. Bachoo, D. H. Rowitch, D. N. Louis, W. K. Cavenee, and R. A. DePinho Malignant glioma: genetics and biology of a grave matter Genes & Dev., June 1, 2001; 15(11): 1311 - 1333. [Full Text] [PDF]
|
|
|
|
|
|
S. Kondraganti, S. Mohanam, S. K. Chintala, Y. Kin, S. L. Jasti, C. Nirmala, S. S. Lakka, Y. Adachi, A. P. Kyritsis, F. Ali-Osman, et al. Selective Suppression of Matrix Metalloproteinase-9 in Human Glioblastoma Cells by Antisense Gene Transfer Impairs Glioblastoma Cell Invasion Cancer Res., December 1, 2000; 60(24): 6851 - 6855. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. KANG, J. YI, W. YANG, X. WANG, A. JIANG, and D. PEI Functional characterization of MT3-MMP in transfected MDCK cells: progelatinase A activation and tubulogenesis in 3-D collagen lattice FASEB J, December 1, 2000; 14(15): 2559 - 2568. [Abstract] [Full Text]
|
|
|
|
|
|
K. Nabeshima, T. Inoue, Y. Shimao, Y. Okada, Y. Itoh, M. Seiki, and M. Koono Front-Cell-specific Expression of Membrane-Type 1 Matrix Metalloproteinase and Gelatinase A during Cohort Migration of Colon Carcinoma Cells Induced by Hepatocyte Growth Factor/Scatter Factor Cancer Res., July 1, 2000; 60(13): 3364 - 3369. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. Hotary, E. Allen, A. Punturieri, I. Yana, and S. J. Weiss Regulation of Cell Invasion and Morphogenesis in a Three-dimensional Type I Collagen Matrix by Membrane-type Matrix Metalloproteinases 1, 2, and 3 J. Cell Biol., June 12, 2000; 149(6): 1309 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nakamura, Y. Fujii, I. Inoki, K. Sugimoto, K. Tanzawa, H. Matsuki, R. Miura, Y. Yamaguchi, and Y. Okada Brevican Is Degraded by Matrix Metalloproteinases and Aggrecanase-1 (ADAMTS4) at Different Sites J. Biol. Chem., December 1, 2000; 275(49): 38885 - 38890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Iida, D. Pei, T. Kang, M. A. Simpson, M. Herlyn, L. T. Furcht, and J. B. McCarthy Melanoma Chondroitin Sulfate Proteoglycan Regulates Matrix Metalloproteinase-dependent Human Melanoma Invasion into Type I Collagen J. Biol. Chem., May 25, 2001; 276(22): 18786 - 18794. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
