Macrophage Elastase (Matrix Metalloproteinase-12) Suppresses Growth of Lung Metastases

Houghton, A. McGarry; Grisolano, Jay L.; Baumann, Mary; Kobayashi, Dale K.; Hautamaki, R. Dean; Nehring, Leslie; Cornelius, Lynn A.; Shapiro, Steven D.

doi:10.1158/0008-5472.can-04-0297

Cited by 156 publications

(108 citation statements)

References 45 publications

(44 reference statements)

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…However, the pro-angiogenic role of MMPs has been challenged by the recent findings that some MMPs (MMP2/3/7/9/12/13/14/20) can process and generate angiogenesis inhibitors like angiostatin or endostatin to inhibit endothelial cell proliferation, migration, and angiogenesis. [38][39][40][41][42] The role of MMP19 in cancer is as controversial as for all other MMPs. MMP19 is up-regulated in astroglial tumor and melanoma 43,44 and reported to increase human keratinocyte cell proliferation, migration, and adhesion on type I collagen through the IGF-signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Catalytic activity of matrix metalloproteinase‐19 is essential for tumor suppressor and anti‐angiogenic activities in nasopharyngeal carcinoma

Chan

Lung

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

The association of Matrix metalloproteinase-19 (MMP19) in the development of nasopharyngeal carcinoma (NPC) was identified from differential gene profiling, which showed MMP19 was one of the candidate genes down-regulated in the NPC cell lines. In this study, quantitative RT-PCR and Western blot analysis showed MMP19 was down-regulated in all seven NPC cell lines. By tissue microarray immunohistochemical staining, MMP19 appears down-regulated in 69.7% of primary NPC specimens. Allelic deletion and promoter hypermethylation contribute to MMP19 down-regulation. We also clearly demonstrate that the catalytic activity of MMP19 plays an important role in antitumor and antiangiogenesis activities in comparative studies of the wild-type and the catalytically inactive mutant MMP19. In the in vivo tumorigenicity assay, only the wild-type (WT), but not mutant, MMP19 transfectants suppress tumor formation in nude mice. In the in vitro colony formation assay, WT MMP19 dramatically reduces colony-forming ability of NPC cell lines, when compared to the inactive mutant. In the tube formation assay of human umbilical vein endothelial cells and human microvascular endothelial cells (HMEC-1), secreted WT MMP19, but not mutant MMP19, induces reduction of tube-forming ability in endothelial cells with decreased vascular endothelial growth factor (VEGF) in conditioned media detected by enzyme-linked immunosorbent assay (ELISA). The anti-angiogenic activity of WT MMP19 is correlated with suppression of tumor formation. These results now clearly show that catalytic activity of MMP19 is essential for its tumor suppressive and anti-angiogenic functions in NPC.Nasopharyngeal carcinoma (NPC) is a malignancy arising from the epithelial cells of the nasopharynx. This cancer has a unique racial and geographic distribution with a high incidence in Southern China and Southeast Asia among the Southern Chinese population. 1 The etiology of NPC is believed to be multifactorial including dietary and

show abstract

Section: Discussionmentioning

confidence: 99%

Catalytic activity of matrix metalloproteinase‐19 is essential for tumor suppressor and anti‐angiogenic activities in nasopharyngeal carcinoma

Chan

Lung

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Converting structural matrix proteins to signalling molecules* • Collagen II: fragment is a bone morphogenetic protein (BMP) antagonist 125,126 • Collagen IV α1-α6 noncollagenous-1 (NC1) domains are anti-angiogenic after cleavage 121,124,127 • Collagen 18 has an NC1 domain (endostatin), which is anti-angiogenic 121,128 Structural changes to matrix proteins…”

Section: Box 2 Biological Consequences Of Mmp Proteolysismentioning

confidence: 99%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

2,558

2,180

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

“…Furthermore, interferon-c, a prominent product of CD8-positive cells, causes emphysema with alveolar enlargement, increased lung volume, enhanced pulmonary compliance, and macrophage-and neutrophil-rich inflammation; this occurs at least in part by the induction and activation of MMP12 [97]. Increased MMP12 activity leads to degradation of elastin, and the resultant monocyte chemotactic fragments further contribute to recruitment of eosinophils and macrophages [98] and to amplification of the inflammatory cascade [42]. Guinea pigs exposed daily to cigarette smoke for up to 6 months were protected from emphysema by the dual MMP9/MMP12 inhibitor, AZ11557272 [51].…”

Section: Dysregulation Of Mmps In Different Lung Disorders and Its Thmentioning

confidence: 99%

A therapeutic role for matrix metalloproteinase inhibitors in lung diseases?

Vandenbroucke¹,

Dejonckheere²,

Libert³

2011

European Respiratory Journal

111

105

View full text Add to dashboard Cite

Disruption of the balance between matrix metalloproteinases (MMPs) and their endogenous inhibitors is considered a key event in the development of pulmonary diseases such as chronic obstructive pulmonary disease, asthma, interstitial lung diseases and lung cancer. This imbalance often results in elevated net MMP activity, making MMP inhibition an attractive therapeutic strategy. Although promising results have been obtained, the lack of selective MMP inhibitors, together with limited knowledge regarding the exact functions of a particular MMP, hampers clinical application. This review discusses the involvement of different MMPs in lung disorders and future opportunities and limitations of therapeutic MMP inhibition.

show abstract

Macrophage Elastase (Matrix Metalloproteinase-12) Suppresses Growth of Lung Metastases

Cited by 156 publications

References 45 publications

Catalytic activity of matrix metalloproteinase‐19 is essential for tumor suppressor and anti‐angiogenic activities in nasopharyngeal carcinoma

Catalytic activity of matrix metalloproteinase‐19 is essential for tumor suppressor and anti‐angiogenic activities in nasopharyngeal carcinoma

Matrix metalloproteinases and the regulation of tissue remodelling

A therapeutic role for matrix metalloproteinase inhibitors in lung diseases?

Contact Info

Product

Resources

About