MT1-MMP–dependent, apoptotic remodeling of unmineralized cartilage

Holmbeck, Kenn; Bianco, Paolo; Chrysovergis, Kaliopi; Yamada, Susan S.; Birkedal‐Hansen, Henning

doi:10.1083/jcb.200307061

Cited by 134 publications

(121 citation statements)

References 40 publications

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…The pseudo-metamorphic form of bone development was discovered only after aberrant residual cartilaginous tissues were found in Mmp14 mutants 45 . In wild-type mice, some skull bones and the diaphysis of long bones are formed by osteoblasts that lay down mineralized bone in close apposition to pre-existing cartilage that functions as a mould and later undergoes apoptosis.…”

Section: Mmp14 Deficiency Results In Lethalitymentioning

confidence: 99%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

2,505

2,119

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease. Despite intensive scrutiny in vitro, in cell culture and in animal models, the normal physiological roles of these extracellular proteases have been elusive. Recent studies in mice and flies point to essential roles of MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or disease associated.The founding member of the matrix metalloproteinase (MMP) family, collagenase, was identified in 1962 by Gross and Lapiere, who found that tadpole tails during metamorphosis contained an enzyme that could degrade fibrillar collagen 1,2 . Subsequently, an interstitial collagenase, collagenase-1 or MMP1, was found in diseased skin and synovium 3 . In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775-Ile776 or Gly775-Lys776 in native type I, II or III collagen molecules 3,4 . Further research led to the discovery of a family of structurally related proteinases (23 in human, 24 in mice), now referred to as the MMP family.Interest in MMPs increased in the late 1960s and early 1970s following observations that MMPs are upregulated in diverse human diseases including rheumatoid arthritis and cancer. Importantly, high levels of MMPs often correlated with poor prognosis in human patients (reviewed in REF. 5 ). However, recent clinical data indicate that the relationship between § These authors contributed equally to this paper. Competing interests statementThe authors declare no competing financial interests. DATABASESThe following terms in this article are linked online to: Entrez Genome: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene DmMmp1 | DmMmp2 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMMPs and disease is not simple; for example, increased MMP activity can enhance tumour progression or can inhibit it (reviewed in REF. 6 ). This complex relationship between MMP expression and cancer has increased the basic and clinical interest in understanding MMP function in vivo, but it has also focused attention on MMPs and pathology, and relatively less attention has been focused on the normal roles of these enzymes. MMP proteolysisMMPs are members of the metzincin group of proteases, which are named after the zinc ion and the conserved Met residue at the active site 11,12 . Recent work has generated a unified peptidase nomenclature 13 Functions of MMP proteolysisHistorically, MMPs were thought to function mainly as enzymes that degrade structural components of the ECM. However, MMP proteolysis can create space for cells to migrate, can produce specific substrate-cleavage fragments with independent biological activity, can MMPs in bone modelling and remodellingBone is an important site of ongoing tissue remodelling during development...

show abstract

Section: Mmp14 Deficiency Results In Lethalitymentioning

confidence: 99%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

2,505

2,119

View full text Add to dashboard Cite

show abstract

“…The notion that MT1-MMP expression may suppress cell proliferation in certain situations or outright lead to apoptotic demise is documented previously. High levels of MT1-MMP expression are required for apoptotic demise of chondrocytes in the removal of the collagenous scaffold of certain cartilage anlagen during development, demonstrating that MT1-MMP is not exclusively associated with promitogenic activity (Holmbeck et al, 2003). At the same time, the loss of MT1-MMP activity is associated with severely diminished cell proliferation in the collagenous environment of the epiphyseal growth plate (Holmbeck et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

MT1-MMP is required for efficient tumor dissemination in experimental metastatic disease

et al. 2007

View full text Add to dashboard Cite

Membrane-type I matrix metalloproteinase (MT1-MMP) is associated with multiple forms of cancer including mammary cancer. To directly evaluate the significance of MT1-MMP expression in tumor progression and metastasis using a genetically induced cancer model, we crossed MT1-MMP-deficient mice to MMTV-polyoma virus middle T-antigen (PyMT) mice. Expression of PyMT in the MT1-MMP-deficient background consistently resulted in hyperplasia of the mammary gland as seen in wild-type PyMT littermates. Following orthotopic transplantation of PyMT þ glands into the cleared mammary fat pad of syngeneic recipient mice, MT1-MMP-deficient tumors were palpable earlier than wild-type tumors. Moreover, MT1-MMP-deficient tumors grew to the experimental end point size quicker than control tumors, but demonstrated markedly reduced ability to metastasize to the lungs of recipient mice. Accordingly, MT1-MMPdeficient mice displayed an overall reduction in metastasis count of 50%. MT1-MMP was expressed solely in the stroma of PyMT-induced tumors and those metastatic nodules that formed in the lungs were devoid of MT1-MMP expression. Stromal fibroblasts isolated from MT1-MMP-deficient tumors did not degrade type I collagen suggesting that efficient dissemination of tumor cells is dependent on stromal cell remodeling of the tumor environment. The data demonstrate directly that MT1-MMP-mediated proteolysis by stromal cells is important in the metastatic process.

show abstract

“…Activated MT1-MMP is a potent membrane proteinase with the ability to cleave type I collagen more efficiently than type II or III collagens [42]. Consistently, MT1-MMP knockout mice are characterized by a defect in cartilage remodeling and bone development [43,44]. Due to their capacity to cleave type I collagen, both MT1-MMP and MT2-MMP are able to endow uninvasive MDCK cells with the ability to penetrate type I collagen matrix [24].…”

Section: Substrates Of Mt-mmpsmentioning

confidence: 96%

Membrane type-matrix metalloproteinases and tumor progression

2005

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that process growth factors, growth factor binding proteins, cell surface proteins, degrade extracellular matrix (ECM) components and thereby play a central role in tissue remodeling and tumor progression. Membrane-type matrix metalloproteinases (MT-MMPs) are a recently discovered subgroup of intrinsic plasma membrane proteins. Their functions have been extended from pericellular proteolysis and control of cell migration to cell signaling, control of cell proliferation and regulation of multiple stages of tumor progression including growth and angiogenesis. This review sheds light on the new functions of MT-MMPs and their inhibitors in tumor development and angiogenesis, and presents recent investigations that document their influence on various cell functions.

show abstract

MT1-MMP–dependent, apoptotic remodeling of unmineralized cartilage

Cited by 134 publications

References 40 publications

Matrix metalloproteinases and the regulation of tissue remodelling

Matrix metalloproteinases and the regulation of tissue remodelling

MT1-MMP is required for efficient tumor dissemination in experimental metastatic disease

Membrane type-matrix metalloproteinases and tumor progression

Contact Info

Product

Resources

About