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Gene Review

MMP2  -  matrix metallopeptidase 2 (gelatinase A,...

Homo sapiens

Synonyms: 72 kDa gelatinase, 72 kDa type IV collagenase, CLG4, CLG4A, Gelatinase A, ...

Disease relevance of MMP2


Psychiatry related information on MMP2


High impact information on MMP2


Chemical compound and disease context of MMP2


Biological context of MMP2


Anatomical context of MMP2

  • We have previously shown that hepatic stellate cells secrete latent MMP2 and that MMP2 activation occurs in coculture of hepatic stellate cells and hepatocytes concomitantly with matrix deposition [26].
  • Zymography demonstrated production of MMP2 and MMP9 by both cell lines, with complete inhibition of these enzymes by BB-94 at 48 ng/mL [27].
  • When incubated with latent MMP2 for times up to 24 h, these membranes activated the enzyme in a time- and dose-dependent manner [28].
  • Expression of MMP2, -7, and -11 was greater in pancreatic carcinoma than in normal pancreas (P < 0.01) [29].
  • Our findings suggest that: 1) the expression of MT1-MMP may influence prognosis via tumor invasion of the gastric wall and lymph node metastasis, and 2) MT1-MMP activation of MMP2 may be clinically relevant in gastric carcinoma tumors [6].

Associations of MMP2 with chemical compounds

  • Actinomycin and cycloheximide inhibited the MMP2 activation induced by concanavalin A [26].
  • RESULTS: Hyperhomocysteinaemia increased the production and enzymatic activity of MMP2 and MMP9, the effect being more pronounced in high glucose [30].
  • Curcumin (1 to 10 microM) reduced the MMP14 expression in both mRNA and protein levels and also inhibited the activity of MMP2, the down-stream gelatinase of MMP14, by gelatin zymographic analysis [31].
  • Exposure of human villous explants of 5 to 8 weeks to a 3% O(2) environment resulted in increased trophoblast outgrowth, cell proliferation, and detection of alpha5 integrin and MMP2, as well as increased activation of FAK in EVT cells compared with explants grown in a 20% O(2) environment [32].
  • OBJECTIVE: Matrix metalloproteinases (MMP), especially the gelatinases (MMP2, MMP9), have been implicated in several features of inflammatory arthritis including angiogenesis and bone erosions [33].

Physical interactions of MMP2

  • In the presence of collagen types I, II, III, V, or gelatin, the rate of inhibition of the 65-kDa MMP-2 by the membrane-bound TIMP-2 decreased considerably [34].
  • 6 nM at the high affinity site, yet neither the MMP-2 45-kDa species nor the CTD interacts with TIMP-1 [35].
  • Thrombospondin type 1 repeats interact with matrix metalloproteinase 2. Regulation of metalloproteinase activity [36].
  • Together, our results provide evidence that MMP-2 is an important determinant of cancer cell behavior but is not inhibited by the collagen binding segment of fibronectin [37].
  • The expression of MT1-MMP also induced binding of gelatinase A to the cell surface by functioning as a receptor [38].

Enzymatic interactions of MMP2

  • The closely related 92-kDa gelatinase/type IV collagenase (MMP-9) is unable to cleave soluble or fibrillar collagen under identical conditions indicating that the specific collagenolytic activity of MMP-2 is not a general property of gelatinases [39].
  • GL-A activation is mediated by a membrane-type MMP (MT-MMP) that cleaves the GL-A propeptide [40].
  • MMP-2 cleaves at the same Gly-Ile/Leu bond in the collagen alpha chains as interstitial collagenases with kcat and Km values similar to that of MMP-1 [39].
  • Furin-cleaved MMP-2 does not possess proteolytic activity as examined in a cell-free assay [41].
  • The chimeric envelope was expressed and incorporated into viral particles, and the EGF domain could be cleaved from the surface of the viral particles by gelatinase A (MMP-2) [42].

Co-localisations of MMP2

  • MMP-2 was colocalized with MT1-MMP and TIMP-2, which are an activator and an activation-enhancing factor, respectively, for proMMP-2 [43].
  • This coincided with MMP-2 induction that co-localized with EMMPRIN at the epithelio-stromal boundary [44].
  • 5. TIMP-4 co-localized with MMP-2 in resting platelets and was released upon platelet aggregation induced by collagen and thrombin [45].

Regulatory relationships of MMP2

  • Given the ability of MT1-MMP to activate MMP-2 and MMP-13, the findings also point to a cooperation between fibroblasts and macrophages in degrading cartilage and bone [46].
  • Subsequently, the MMP-2.TIMP-2 complex is released from the membrane, and the activity of MMP-2 is blocked by TIMP-2 [34].
  • Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases [47].
  • Adhesion of Jurkat cells to the second major alpha(4)beta(1) ligand, VCAM-1, upregulated mRNA for MMP-2 (3.5-fold) and failed to induce expression of mRNA for MMP-9 [48].
  • Because of its dual ability to activate MMP-2 and to up-regulate VEGF, MT1-MMP might be of central importance in the growth of GBMs and represent an interesting target for anti-cancer treatments [49].

Other interactions of MMP2


Analytical, diagnostic and therapeutic context of MMP2


  1. Cyclic AMP-regulated synthesis of the tissue inhibitors of metalloproteinases suppresses the invasive potential of the human fibrosarcoma cell line HT1080. Tanaka, K., Iwamoto, Y., Ito, Y., Ishibashi, T., Nakabeppu, Y., Sekiguchi, M., Sugioka, Y. Cancer Res. (1995) [Pubmed]
  2. Torg syndrome is caused by inactivating mutations in MMP2 and is allelic to NAO and Winchester syndrome. Zankl, A., Pachman, L., Poznanski, A., Bonafé, L., Wang, F., Shusterman, Y., Fishman, D.A., Superti-Furga, A. J. Bone. Miner. Res. (2007) [Pubmed]
  3. Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas. Théret, N., Musso, O., Turlin, B., Lotrian, D., Bioulac-Sage, P., Campion, J.P., Boudjéma, K., Clément, B. Hepatology (2001) [Pubmed]
  4. Expression of MMP2, MMP9, MT1-MMP, TIMP1, and TIMP2 mRNA in valvular lesions of the heart. Soini, Y., Satta, J., Määttä, M., Autio-Harmainen, H. J. Pathol. (2001) [Pubmed]
  5. Substantial reduction in risk of breast cancer associated with genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 genes. Zhou, Y., Yu, C., Miao, X., Tan, W., Liang, G., Xiong, P., Sun, T., Lin, D. Carcinogenesis (2004) [Pubmed]
  6. Analysis of MT1-MMP and MMP2 expression in human gastric cancers. Mori, M., Mimori, K., Shiraishi, T., Fujie, T., Baba, K., Kusumoto, H., Haraguchi, M., Ueo, H., Akiyoshi, T. Int. J. Cancer (1997) [Pubmed]
  7. Interaction between cancer cells and stromal fibroblasts is required for activation of the uPAR-uPA-MMP-2 cascade in pancreatic cancer metastasis. He, Y., Liu, X.D., Chen, Z.Y., Zhu, J., Xiong, Y., Li, K., Dong, J.H., Li, X. Clin. Cancer Res. (2007) [Pubmed]
  8. Activated isoforms of MMP-2 are induced in U87 human glioma cells in response to beta-amyloid peptide. Deb, S., Zhang, J.W., Gottschall, P.E. J. Neurosci. Res. (1999) [Pubmed]
  9. Crucial role of inhibitor of DNA binding/differentiation in the vascular endothelial growth factor-induced activation and angiogenic processes of human endothelial cells. Sakurai, D., Tsuchiya, N., Yamaguchi, A., Okaji, Y., Tsuno, N.H., Kobata, T., Takahashi, K., Tokunaga, K. J. Immunol. (2004) [Pubmed]
  10. Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia. Conant, K., McArthur, J.C., Griffin, D.E., Sjulson, L., Wahl, L.M., Irani, D.N. Ann. Neurol. (1999) [Pubmed]
  11. Increased fibronectin expression in lung in the setting of chronic alcohol abuse. Burnham, E.L., Moss, M., Ritzenthaler, J.D., Roman, J. Alcohol. Clin. Exp. Res. (2007) [Pubmed]
  12. Matrix metalloproteinase inhibitor RO 28-2653 decreases liver metastasis by reduction of MMP-2 and MMP-9 concentration in BOP-induced ductal pancreatic cancer in Syrian Hamsters: Inhibition of matrix metalloproteinases in pancreatic cancer. Kilian, M., Gregor, J.I., Heukamp, I., Hanel, M., Ahlgrimm, M., Schimke, I., Kristiansen, G., Ommer, A., Walz, M.K., Jacobi, C.A., Wenger, F.A. Prostaglandins Leukot. Essent. Fatty Acids (2006) [Pubmed]
  13. Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome. Martignetti, J.A., Aqeel, A.A., Sewairi, W.A., Boumah, C.E., Kambouris, M., Mayouf, S.A., Sheth, K.V., Eid, W.A., Dowling, O., Harris, J., Glucksman, M.J., Bahabri, S., Meyer, B.F., Desnick, R.J. Nat. Genet. (2001) [Pubmed]
  14. Don't mess with the matrix. Vu, T.H. Nat. Genet. (2001) [Pubmed]
  15. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Brooks, P.C., Strömblad, S., Sanders, L.C., von Schalscha, T.L., Aimes, R.T., Stetler-Stevenson, W.G., Quigley, J.P., Cheresh, D.A. Cell (1996) [Pubmed]
  16. Prognostic significance of matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression in prostate cancer. Ross, J.S., Kaur, P., Sheehan, C.E., Fisher, H.A., Kaufman, R.A., Kallakury, B.V. Mod. Pathol. (2003) [Pubmed]
  17. Lysophosphatidic acid enhances epithelial ovarian carcinoma invasion through the increased expression of interleukin-8. So, J., Navari, J., Wang, F.Q., Fishman, D.A. Gynecol. Oncol. (2004) [Pubmed]
  18. Phosphoinositide 3-kinase regulates membrane Type 1-matrix metalloproteinase (MMP) and MMP-2 activity during melanoma cell vasculogenic mimicry. Hess, A.R., Seftor, E.A., Seftor, R.E., Hendrix, M.J. Cancer Res. (2003) [Pubmed]
  19. Autocrine/paracrine prostaglandin E2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD44 in cyclooxygenase-2-dependent invasion. Dohadwala, M., Batra, R.K., Luo, J., Lin, Y., Krysan, K., Pold, M., Sharma, S., Dubinett, S.M. J. Biol. Chem. (2002) [Pubmed]
  20. Expression of matrix metalloproteinase 2 (MMP-2), membrane-type 1 MMP and tissue inhibitor of metalloproteinase 2 and activation of proMMP-2 in pancreatic duct adenocarcinomas in hamsters treated with N-nitrosobis(2-oxopropyl)amine. Iki, K., Tsutsumi, M., Kido, A., Sakitani, H., Takahama, M., Yoshimoto, M., Motoyama, M., Tatsumi, K., Tsunoda, T., Konishi, Y. Carcinogenesis (1999) [Pubmed]
  21. Platelet release of trimolecular complex components MT1-MMP/TIMP2/MMP2: involvement in MMP2 activation and platelet aggregation. Kazes, I., Elalamy, I., Sraer, J.D., Hatmi, M., Nguyen, G. Blood (2000) [Pubmed]
  22. S100A4 involvement in metastasis: deregulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in osteosarcoma cells transfected with an anti-S100A4 ribozyme. Bjørnland, K., Winberg, J.O., Odegaard, O.T., Hovig, E., Loennechen, T., Aasen, A.O., Fodstad, O., Maelandsmo, G.M. Cancer Res. (1999) [Pubmed]
  23. Oxidative stress stimulates proliferation and invasiveness of hepatic stellate cells via a MMP2-mediated mechanism. Galli, A., Svegliati-Baroni, G., Ceni, E., Milani, S., Ridolfi, F., Salzano, R., Tarocchi, M., Grappone, C., Pellegrini, G., Benedetti, A., Surrenti, C., Casini, A. Hepatology (2005) [Pubmed]
  24. Activation of platelet-activating factor receptor-coupled G alpha q leads to stimulation of Src and focal adhesion kinase via two separate pathways in human umbilical vein endothelial cells. Deo, D.D., Bazan, N.G., Hunt, J.D. J. Biol. Chem. (2004) [Pubmed]
  25. Down-regulation of glomerular matrix metalloproteinase-2 gene in human NIDDM. Del Prete, D., Anglani, F., Forino, M., Ceol, M., Fioretto, P., Nosadini, R., Baggio, B., Gambaro, G. Diabetologia (1997) [Pubmed]
  26. MMP2 activation by collagen I and concanavalin A in cultured human hepatic stellate cells. Théret, N., Lehti, K., Musso, O., Clément, B. Hepatology (1999) [Pubmed]
  27. Effect of matrix metalloproteinase inhibition on pancreatic cancer invasion and metastasis: an additive strategy for cancer control. Jimenez, R.E., Hartwig, W., Antoniu, B.A., Compton, C.C., Warshaw, A.L., Fernández-Del Castillo, C. Ann. Surg. (2000) [Pubmed]
  28. Induction of metalloproteinases by glomerular mesangial cells stimulated by proteins of the extracellular matrix. Martin, J., Eynstone, L., Davies, M., Steadman, R. J. Am. Soc. Nephrol. (2001) [Pubmed]
  29. Imbalance of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of the matrix metalloproteinases (TIMPs) in human pancreatic carcinoma. Bramhall, S.R., Neoptolemos, J.P., Stamp, G.W., Lemoine, N.R. J. Pathol. (1997) [Pubmed]
  30. High glucose and homocysteine synergistically affect the metalloproteinases-tissue inhibitors of metalloproteinases pattern, but not TGFB expression, in human fibroblasts. Solini, A., Santini, E., Nannipieri, M., Ferrannini, E. Diabetologia (2006) [Pubmed]
  31. Anti-invasive gene expression profile of curcumin in lung adenocarcinoma based on a high throughput microarray analysis. Chen, H.W., Yu, S.L., Chen, J.J., Li, H.N., Lin, Y.C., Yao, P.L., Chou, H.Y., Chien, C.T., Chen, W.J., Lee, Y.T., Yang, P.C. Mol. Pharmacol. (2004) [Pubmed]
  32. Focal adhesion kinase is a key mediator of human trophoblast development. MacPhee, D.J., Mostachfi, H., Han, R., Lye, S.J., Post, M., Caniggia, I. Lab. Invest. (2001) [Pubmed]
  33. Gelatinase expression and activity in the synovium and skin of patients with erosive psoriatic arthritis. Hitchon, C.A., Danning, C.L., Illei, G.G., El-Gabalawy, H.S., Boumpas, D.T. J. Rheumatol. (2002) [Pubmed]
  34. Plasma membrane-bound tissue inhibitor of metalloproteinases (TIMP)-2 specifically inhibits matrix metalloproteinase 2 (gelatinase A) activated on the cell surface. Itoh, Y., Ito, A., Iwata, K., Tanzawa, K., Mori, Y., Nagase, H. J. Biol. Chem. (1998) [Pubmed]
  35. Kinetic analysis of the binding of human matrix metalloproteinase-2 and -9 to tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Olson, M.W., Gervasi, D.C., Mobashery, S., Fridman, R. J. Biol. Chem. (1997) [Pubmed]
  36. Thrombospondin type 1 repeats interact with matrix metalloproteinase 2. Regulation of metalloproteinase activity. Bein, K., Simons, M. J. Biol. Chem. (2000) [Pubmed]
  37. Matrix metalloproteinase-2 contributes to cancer cell migration on collagen. Xu, X., Wang, Y., Chen, Z., Sternlicht, M.D., Hidalgo, M., Steffensen, B. Cancer Res. (2005) [Pubmed]
  38. Membrane-type matrix metalloproteinases (MT-MMPs) in cell invasion. Sato, H., Okada, Y., Seiki, M. Thromb. Haemost. (1997) [Pubmed]
  39. Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. Aimes, R.T., Quigley, J.P. J. Biol. Chem. (1995) [Pubmed]
  40. Gelatinase A activation is regulated by the organization of the polymerized actin cytoskeleton. Tomasek, J.J., Halliday, N.L., Updike, D.L., Ahern-Moore, J.S., Vu, T.K., Liu, R.W., Howard, E.W. J. Biol. Chem. (1997) [Pubmed]
  41. Furin directly cleaves proMMP-2 in the trans-Golgi network resulting in a nonfunctioning proteinase. Cao, J., Rehemtulla, A., Pavlaki, M., Kozarekar, P., Chiarelli, C. J. Biol. Chem. (2005) [Pubmed]
  42. A gene delivery system activatable by disease-associated matrix metalloproteinases. Peng, K.W., Morling, F.J., Cosset, F.L., Murphy, G., Russell, S.J. Hum. Gene Ther. (1997) [Pubmed]
  43. Production and activation of matrix metalloproteinase-2 in proliferative diabetic retinopathy. Noda, K., Ishida, S., Inoue, M., Obata, K., Oguchi, Y., Okada, Y., Ikeda, E. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  44. Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas: role in epithelio-stromal interactions and matrix metalloproteinase induction. Gabison, E.E., Mourah, S., Steinfels, E., Yan, L., Hoang-Xuan, T., Watsky, M.A., De Wever, B., Calvo, F., Mauviel, A., Menashi, S. Am. J. Pathol. (2005) [Pubmed]
  45. Identification, regulation and role of tissue inhibitor of metalloproteinases-4 (TIMP-4) in human platelets. Radomski, A., Jurasz, P., Sanders, E.J., Overall, C.M., Bigg, H.F., Edwards, D.R., Radomski, M.W. Br. J. Pharmacol. (2002) [Pubmed]
  46. Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid arthritis. Pap, T., Shigeyama, Y., Kuchen, S., Fernihough, J.K., Simmen, B., Gay, R.E., Billingham, M., Gay, S. Arthritis Rheum. (2000) [Pubmed]
  47. Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases. Miyamori, H., Takino, T., Kobayashi, Y., Tokai, H., Itoh, Y., Seiki, M., Sato, H. J. Biol. Chem. (2001) [Pubmed]
  48. Differential induction of gelatinase B (MMP-9) and gelatinase A (MMP-2) in T lymphocytes upon alpha(4)beta(1)-mediated adhesion to VCAM-1 and the CS-1 peptide of fibronectin. Yakubenko, V.P., Lobb, R.R., Plow, E.F., Ugarova, T.P. Exp. Cell Res. (2000) [Pubmed]
  49. Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1-MMP, MMP-2 and MMP-9 in human glioblastomas. Munaut, C., Noël, A., Hougrand, O., Foidart, J.M., Boniver, J., Deprez, M. Int. J. Cancer (2003) [Pubmed]
  50. Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. McQuibban, G.A., Gong, J.H., Tam, E.M., McCulloch, C.A., Clark-Lewis, I., Overall, C.M. Science (2000) [Pubmed]
  51. The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression. Lara-Pezzi, E., Gómez-Gaviro, M.V., Gálvez, B.G., Mira, E., Iñiguez, M.A., Fresno, M., Martínez-A, C., Arroyo, A.G., López-Cabrera, M. J. Clin. Invest. (2002) [Pubmed]
  52. Progesterone regulates the activity of collagenase and related gelatinases A and B in human endometrial explants. Marbaix, E., Donnez, J., Courtoy, P.J., Eeckhout, Y. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  53. Evidence for altered balance between matrix metalloproteinases and their inhibitors in human aortic diseases. Knox, J.B., Sukhova, G.K., Whittemore, A.D., Libby, P. Circulation (1997) [Pubmed]
  54. Membrane-type matrix metalloproteinase-mediated angiogenesis in a fibrin-collagen matrix. Collen, A., Hanemaaijer, R., Lupu, F., Quax, P.H., van Lent, N., Grimbergen, J., Peters, E., Koolwijk, P., van Hinsbergh, V.W. Blood (2003) [Pubmed]
  55. Role of discoidin domain receptors 1 and 2 in human smooth muscle cell-mediated collagen remodeling: potential implications in atherosclerosis and lymphangioleiomyomatosis. Ferri, N., Carragher, N.O., Raines, E.W. Am. J. Pathol. (2004) [Pubmed]
  56. Metalloproteinase expression and prognosis in soft tissue sarcomas. Benassi, M.S., Gamberi, G., Magagnoli, G., Molendini, L., Ragazzini, P., Merli, M., Chiesa, F., Balladelli, A., Manfrini, M., Bertoni, F., Mercuri, M., Picci, P. Ann. Oncol. (2001) [Pubmed]
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