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Z Gastroenterol 2001; 39(9): 807-813
DOI: 10.1055/s-2001-17197
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© Karl Demeter Verlag im Georg Thieme Verlag Stuttgart · New York

Matrixmetalloproteinasen als Promotoren der Tumorinvasion und Metastasierung

Eine Übersicht unter besonderer Berücksichtigung des GastrointestinaltraktesMatrix metalloproteinases: Promoters of tumor invasion and metastasis - A review with focus on gastrointestinal tumorsE. Roeb, S. Matern
  • Medizinische Klinik III Universitätsklinikum der RWTH Aachen
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Publikationsverlauf

1.12.2000

18.1.2001

Publikationsdatum:
14. September 2001 (online)

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Zusammenfassung

Die Degradation von Basalmembran und extrazellulärer Matrix ist eine Voraussetzung für die Invasion und Metastasierung von Tumorzellen. Die dazu erforderliche Proteolyse erfolgt unter anderem durch Matrixmetalloproteinasen und ist streng kontrolliert durch spezifische endogene Proteaseinhibitoren.

Dieser Review fasst den gegenwärtigen Stand der Erkenntnisse über die Rolle der Matrixmetalloproteinasen im Wachstum, der Invasion und Metastasierung zusammen und fokussiert sich auf die Bedeutung der Matrixmetalloproteinasen bei gastrointestinalen Tumoren.

Matrix metalloproteinases: Promoters of tumor invasion and metastasis - A review with focus on gastrointestinal tumors

Degradation of basement membrane and extracellular matrix is crucial for invasion and metastasis of tumor cells. Proteolysis occurs via matrix metalloproteinases and is tightly controlled by specific endogenous proteinase inhibitors.

This review will summarize the current view on the role of matrix metalloproteinases in tumor growth, invasion and metastasis and focus on the importance of matrix metalloproteinases in gastrointestinal cancer.

Schlüsselwörter

Matrixmetalloproteinasen - TIMP - Kolonkarzinom - Invasion - Metastasierung

Key words

Matrix Metalloproteinases - TIMP - Colon Carcinom - Invasion - Metastasis

Literatur

  • 1 Kähäri V M, Saarialho-Kere U. Matrix metalloproteinases in skin.  Exp Dermatol. 1997;  6 199-213
    Suche in Google Scholar
  • 2 Shapiro S D. Matrix metalloproteinase degradation of extracellular matrix: Biological consequences.  Curr Opin Cell Biol. 1998;  10 602-608
    Suche in Google Scholar
  • 3 Woessner JF. The matrix metalloproteinase family. Parks WC, Mecham RP Matrix, Metalloproteinases San Diego; Academic Press 1998: 1-14
    Suche in Google Scholar
  • 4 Basset P, Okada A, Chenard M P. et al . Matrix metalloproteinases as stromal effectors of human carcinoma progression: Therapeutical implications.  Matrix Biol. 1997;  15 535-541
    Suche in Google Scholar
  • 5 Johnsen M, Lund L R, Romer J, Almholt K, Danø K. Cancer invasion and tissue remodeling: Common themes in proteolytic matrix degradation.  Curr Opin Cell Biol. 1998;  10 667-671
    Suche in Google Scholar
  • 6 Westermarck J, Kähäri V M. Regulation of matrix metalloproteinase expression in tumor invasion.  FASEB J. 1999;  13 781-792
    Suche in Google Scholar
  • 7 Murphy G, Knäuper V. Relating matrix metalloproteinase structure to function: Why the ‘hemopexin’ domain?.  Matrix Biol. 1997;  15 511-518
    Suche in Google Scholar
  • 8 Gomez D E, Alonso D F, Yoshiji H, Thorgeirsson U P. Tissue inhibitors of metalloproteinases: Structure, regulation and biological functions.  Eur J Cell Biol. 1997;  74 111-122
    Suche in Google Scholar
  • 9 Hanemaaijer R, Sorsa T, Konttinen Y T. et al . Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells. Regulation by tumor necrosis factor- and doxycycline.  J Biol Chem. 1997;  272 31 504-31 509
    Suche in Google Scholar
  • 10 Kruger A, Sanchez Sweatman O H, Martin D C. et al . Host TIMP-1 overexpression confers resistance to experimental brain metastasis of a fibrosarcoma cell line.  Oncogene. 1998;  16 2419-2423
    Suche in Google Scholar
  • 11 Ahonen M, Baker A, Kähäri V M. Adenovirus-mediated gene delivery of tissue inhibitor of metalloproteinases-3 inhibits invasion and induces apoptosis in melanoma cells.  Cancer Res. 1998;  58 2310-2315
    Suche in Google Scholar
  • 12 Pilcher B, Dumin J, Sudbeck B. et al . The activity of collagenase-1 is required for keratinocyte migration on a type I collagen matrix.  J Cell Biol. 1997;  137 1445-1457
    Suche in Google Scholar
  • 13 Koop S, Khokha R, Schmidt E E. et al . Overexpression of metalloproteinase inhibitor in B16F10 cells does not affect extravasation but reduces tumor growth.  Cancer Res. 1994;  54 4791-4797
    Suche in Google Scholar
  • 14 Kim J, Yu W, Kovalski K, Ossowski L. Requirement of specific proteases in cancer cell intravasation as revealed by novel semiquantitative PCR-based assay.  Cell. 1998;  94 353-362
    Suche in Google Scholar
  • 15 Brooks P C, Silletti S, von Schalscha T L, Friedlander M, Cheresh D A. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity.  Cell. 1998;  92 391-400
    Suche in Google Scholar
  • 16 Wilson C L, Heppner K J, Labosky P A, Hogan B L, Matrisian L M. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin.  Proc Natl Acad Sci USA. 1997;  94 1402-1407
    Suche in Google Scholar
  • 17 Itoh T, Tanioka M, Yoshida H. et al . Reduced angiogenesis and tumor progression in gelatinase A-deficient mice.  Cancer Res. 1998;  58 1048-1051
    Suche in Google Scholar
  • 18 Masson R, Lefebvre O, Noel A. et al . In vivo evidence that the stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy.  J Cell Biol. 1998;  140 1535-1541
    Suche in Google Scholar
  • 19 Uría J A, Ståhle-Bäckdahl M, Seiki M, Fueyo A, López-Otín C. Regulation of collagenase-3 expression in human breast carcinomas is mediated by stromal-epithelial cell interactions.  Cancer Res. 1997;  57 4882-4888
    Suche in Google Scholar
  • 20 Johansson N, Vaalamo M, Grénman S. et al . Collagenase-3 (MMP-13) is expressed by tumor cells in invasive vulvar squamous cell carcinomas.  Am J Pathol. 1999;  154 469-480
    Suche in Google Scholar
  • 21 Guo H, Zucker S, Gordon M K, Toole B P, Biswas C. Stimulation of matrix metalloproteinase production by recombinant extracellular matrix metalloproteinase inducer from transfected Chinese hamster ovary cells.  J Biol Chem. 1997;  272 24-27
    Suche in Google Scholar
  • 22 Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis.  Cell. 1996;  86 353-364
    Suche in Google Scholar
  • 23 Iozzo R V. Tumor stroma as a regulator of neoplastic behavior. Agonistic and antagonistic elements embedded in the same connective tissue.  Lab Invest. 1995;  73 157-160
    Suche in Google Scholar
  • 24 Heppner K J, Matrisian L M, Jensen R A, Rodgers W H. Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response.  Am J Pathol. 1996;  149 273-282
    Suche in Google Scholar
  • 25 Ståhle-Bäckdahl M, Parks W C. 92-kd gelatinase is actively expressed by eosinophils and stored by neutrophils in squamous cell carcinoma.  Am J Pathol. 1993;  142 995-1000
    Suche in Google Scholar
  • 26 Moll U M, Youngleib G, Rosinski K, Quigley J P. Tumor promoter-stimulated Mr 92,000 gelatinase secreted by normal and malignant human cells: Isolation and characterization of the enzyme from HT1080 tumor cells.  Cancer Res. 1990;  50 6162-6170
    Suche in Google Scholar
  • 27 Unemori E, Hibbs M S, Armento E P. Constitutive expression of a 92-kD gelatinase (type V collagenase) by rheumatoid synovial fibroblasts and its induction in normal human fibroblasts by inflammatory cytokines.  J Clin Invest. 1991;  88 1656-1662
    Suche in Google Scholar
  • 28 Kondapaka S B, Fridman R, Reddy K B. Epidermal growth factor and amphiregulin up-regulate matrix metalloproteinase-9 (MMP-9) in human breast cancer cells.  Int J Cancer. 1997;  70 722-726
    Suche in Google Scholar
  • 29 Partridge C A, Phillips P G, Niedbala M J, Jeffrey J J. Localization and activation of type IV collagenase/gelatinase at endothelial focal contacts.  Am J Physiol. 1997;  272 L813-L822
    Suche in Google Scholar
  • 30 Himelstein B P, Conte-Soler R, Bernhard E J, Dilks D W, Muschel R J. Metalloproteinases in tumor progression: The contribution of MMP-9.  Invasion Metastasis. 1994;  14 246-258
    Suche in Google Scholar
  • 31 Ramos-DeSimone N, Hahn-Dantona E. et al . Activation of matrix metalloproteinase-9 (MMP-9) via a converging plasmin/stromelysin-1 cascade enhances tumor cell invasion.  J Biol Chem. 1999;  274 13 066-13 076
    Suche in Google Scholar
  • 32 Vu T H, Shipley J M, Bergers G. et al . MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes.  Cell. 1998;  93 411-422
    Suche in Google Scholar
  • 33 Murray G I, Duncan M E, O’Neil P, Melvin W T, Fothergill J E. Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer.  Nat Med. 1996;  2 461-462
    Suche in Google Scholar
  • 34 Sier C F, Kubben F J, Ganesh S. et al . Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma.  Br J Cancer. 1996;  74 413-417
    Suche in Google Scholar
  • 35 Allgayer H, Babic R, Beyer B C. et al . Prognostic relevance of MMP-2 (72-kD collagenase IV) in gastric cancer.  Oncology. 1998;  55 152-160
    Suche in Google Scholar
  • 36 Kumar A, Collins H M, Scholefield J H, Watson S A. Increased type-IV collagenase (MMP-2 and MMP-9) activity following preoperative radiotherapy in rectal cancer.  Br J Cancer. 2000;  82 960-965
    Suche in Google Scholar
  • 37 Blavier L, Henriet P, Imren S, DeClerck Y A. Tissue inhibitors of matrix metalloproteinases in cancer.  Ann N Y Acad Sci. 1999;  878 108-119
    Suche in Google Scholar
  • 38 Tsuchiya Y, Sato H, Endo Y. et al . Tissue inhibitor of metalloproteinase 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line, KKLS, in the chick embryo.  Cancer Res. 1993;  53 1397-1402
    Suche in Google Scholar
  • 39 Watanabe M, Takahashi Y, Ohta T. et al . Inhibition of metastasis in human gastric cancer cells transfected with tissue inhibitor of metalloproteinase 1 gene in nude mice.  Cancer. 1996;  77 1676-1680
    Suche in Google Scholar
  • 40 Azuma M, Tamatani T, Fukui K et al. Role of plasminogen activators, metalloproteinases and the tissue inhibitor of metalloproteinase-1 in the metastatic process of human salivary-gland adenocarcinoma cells.  Int J Cancer. 1993;  54 669-676
    Suche in Google Scholar
  • 41 Mohanam S, Wang S W, Rayford A. et al . Expression of tissue inhibitors of metalloproteinases: Negative regulators of human glioblastoma invasion in vivo.  Clin Exp Metastasis. 1995;  13 57-62
    Suche in Google Scholar
  • 42 Zeng Z S, Cohen A M, Zhang Z F, Stetler-Stevenson W, Guillem J G. Elevated tissue inhibitor of metalloproteinase 1 RNA in colorectal cancer stroma correlates with lymph node and distant metastasis.  Clin Cancer Res. 1995;  1 899-906
    Suche in Google Scholar
  • 43 Mori M, Mimori K, Sadanaga N. et al . Prognostic impact of tissue inhibitor of matrix metallproteinase-1 in esophageal carcinoma.  Int J Cancer. 2000;  88 575-578
    Suche in Google Scholar
  • 44 Docherty A, Lyons A, Smith B. et al . Sequence of human tissue inhibitor of metalloproteinase and its identity to erythroid-potentiating activity.  Nature. 1985;  318 66-69
    Suche in Google Scholar
  • 45 Hayakawa T, Yamashita K, Kishi J, Harigaya K. Tissue inhibitor of metalloproteinases from human bone marrow stromal cell line KM102 has erythroid-potentiating activity, suggesting its possible bifunctional role in the hematopoietic microenvironment.  FEBS Lett. 1990;  268 125-128
    Suche in Google Scholar
  • 46 Hayakawa T, Yamashita K, Tanzawa K, Uchijima E, Iwata K. Growth-promoting activity of tissue inhibitor of metalloproteinases-1 (TIMP-1) for a wide range of cells. A possible new growth factor in serum.  FEBS Lett. 1992;  298 29-32
    Suche in Google Scholar
  • 47 Pyke C, Ralfkiaer E, Tryggvason K, Dano K. Messenger RNA for two type IV collagenases is located in stromal cells in human colon cancer.  Am J Pathol. 1993;  142 359-365
    Suche in Google Scholar
  • 48 Emmert-Buck M R, Roth M J, Zhuang Z. et al . Increased gelatinase A (MMP-2) and cathepsin B activity in invasive tumor regions of human colon cancer samples.  Am J Pathol. 1994;  145 1285-1290
    Suche in Google Scholar
  • 49 Zeng Z S, Guillem J G. Colocalisation of matrix metalloproteinase-9-mRNA and protein in human colorectal cancer stromal cells.  Br J Cancer. 1996;  74 1161-1167
    Suche in Google Scholar
  • 50 Zeng Z S, Huang Y, Cohen A M, Guillem J G. Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9.  J Clin Oncol. 1996;  14 3133-3140
    Suche in Google Scholar
  • 51 Zeng Z S, Cohen A M, Guillem J G. Loss of basement membrane type IV collagen is associated with increased expression of metalloproteinases 2 and 9 (MMP-2 and MMP-9) during human colorectal tumorigenesis.  Carcinogenesis. 1999;  20 749-755
    Suche in Google Scholar
  • 52 Roeb E, Hoor M, Breuer B. et al . Unterschiedliche Expression von MMP-2, MMP-9 und TIMP-1 bei kolorektalen Karzinomen im Vergleich zu gesundem Darmgewebe.  Z Gastroenterol. 1998;  36 715 A
    Suche in Google Scholar
  • 53 Poulsom R, Pignatelli M, Stetler-Stevenson W G. et al . Stromal expression of 72 kda type IV collagenase (MMP-2) and TIMP-2 mRNAs in colorectal neoplasia.  Am J Pathol. 1992;  141 389-396
    Suche in Google Scholar
  • 54 Pyke C, Ralfkiaer E, Tryggvason K, Dano K. Messenger RNA for two type IV collagenases is located in stromal cells in human colon cancer.  Am J Pathol. 1993;  142 359-365
    Suche in Google Scholar
  • 55 Shimizu S, Nishikawa Y, Kuroda K. et al . Involvement of transforming growth factor beta1 in autocrine enhancement of gelatinase B secretion by murine metastatic colon carcinoma cells.  Cancer Res. 1996;  56 3366-3370
    Suche in Google Scholar
  • 56 Tremble P M, Lane T F, Sage E H, Werb Z. SPARC, a secreted protein associated with morphogenesis and tissue remodeling, induces expression of metalloproteinases in fibroblasts through a novel extracellularmatrix-dependent pathway.  J Cell Biol. 1993;  121 1433-1444
    Suche in Google Scholar
  • 57 MacDougall J R, Bani M R, Lin Y, Rak J, Kerbel R S. The 92-kDa gelatinase B is expressed by advanced stage melanoma cells: Suppression by somatic cell hybridization with early stage melanoma cells.  Cancer Res. 1995;  55 4174-4181
    Suche in Google Scholar
  • 58 Lauricella-Lefebvre M A, Castronovo V, Sato H. et al . Stimulation of the 92-kD type IV collagenase promoter and enzyme expression in human melanoma cells.  Invasion Metastasis. 1993;  13 289-300
    Suche in Google Scholar
  • 59 Roeb E, Behrmann I, Grötzinger J, Breuer B, Matern S. A MMP-9 mutant without gelatinolytic activity as a novel TIMP-1-antagonist.  FASEB J. 2000;  14 1671-1673
    Suche in Google Scholar
  • 60 Brooks P C, Silletti S, von Schalscha T L, Friedlander M, Cheresh D A. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity.  Cell. 1998;  92 391-400
    Suche in Google Scholar
  • 61 Brown P D. Synthetic inhibitors of matrix metalloproteinases. Parks WC, Mecham RP Matrix Metalloproteinases San Diego; Academic Press 1998: 243-262
    Suche in Google Scholar
  • 62 Kähäri V M, Saarialho-Kere U. Matrix metalloproteinases and their inhibitors in tumour growth and invasion.  Ann Med. 1999;  31 34-45
    Suche in Google Scholar
  • 63 Macaulay V M, O’Byrne K J, Saunders M P. et al . Phase I study of intrapleural batimastat (BB-94), a matrix metalloproteinase inhibitor, in the treatment of malignant pleural effusions.  Clin Cancer Res. 1999;  5 513-520
    Suche in Google Scholar
  • 64 Brand K, Baker A H, Perez-Canto A. et al . Treatment of colorectal liver metastases by adenoviral transfer of tissue inhibitor of metalloproteinases-2 into the liver tissue.  Cancer Res. 2000;  60 5723-5730
    Suche in Google Scholar
  • 65 Fife R S, Rougraff B T, Proctor C, Sledge G W Jr. Inhibition of proliferation and induction of apoptosis by doxycycline in cultured human osteosarcoma cells.  J Lab Clin Med. 1997;  130 530-534
    Suche in Google Scholar
  • 66 Baker A H, Zaltsman A B, George S J, Newby A C. Divergent effects of tissue inhibitor of metalloproteinase-1, -2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro: TIMP-3 promotes apoptosis.  J Clin Invest. 1998;  101 1478-1487
    Suche in Google Scholar
  • 67 Stetler-Stevenson W G. Matrix metalloproteinases in angiogenesis: A moving target for therapeutic intervention.  J Clin Invest. 1999;  103 1237-1241
    Suche in Google Scholar
  • 68 Nelson A R, Fingleton B, Rothenberg M L, Matrisian L M. Matrix metalloproteinases: Biologic activity and clinical implications.  J Clin Oncol. 2000;  18 1135-1149
    Suche in Google Scholar
  • 69 Kerkela E, Ala-Aho R, Jeskanen L. et al . Expression of human macrophage metalloelastase (MMP-12) by tumor cells in skin cancer.  J Invest Dermatol. 2000;  114 1113-1119
    Suche in Google Scholar
  • 70 Velasco G, Cal S, Merlos-Suarez A. et al . Human MT6-matrix metalloproteinase: Identification, progelatinase A activation, and expression in brain tumors.  Cancer Res. 2000;  60 877-882
    Suche in Google Scholar

Anschrift für die Verfasser

PD Dr. Elke Roeb

Medizinische Klinik III
Universitätsklinikum der RWTH Aachen

Pauwelsstraße 30

52057 Aachen

eMail: elke.roeb@post.klinikum.rwth-aachen.de