Diet-Induced Obesity and Reduced Skin Cancer Susceptibility in Matrix Metalloproteinase 19-Deficient Mice

Pendás, Alberto M.; Folgueras, Alicia R.; Llano, Elena; Caterina, John J.; Frerard, Françoise; Rodríguez, Francisco; Astudillo, Aurora; Noël, Agnès; Birkedal‐Hansen, Henning; López-Otı́n, Carlos

doi:10.1128/mcb.24.12.5304-5313.2004

Cited by 91 publications

(68 citation statements)

References 42 publications

(51 reference statements)

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“…-/-) mice were generated as previously described (18,32). Six to eight weeks-old males were sensitized by intraperitoneal injection of ovalbumin (OVA) (Sigma Aldrich, Schnelldorf, Germany) emulsified in aluminum hydroxyde (AlumInject; Perbio, Erembodegem, Belgium) on days 1 and 8.…”

Section: Mmp-19 Knock-out (Mmp-19mentioning

confidence: 99%

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Matrix Metalloproteinase-19 Deficiency Promotes Tenascin-C Accumulation and Allergen-Induced Airway Inflammation

Guéders¹,

Hirst²,

Quesada-Calvo³

et al. 2010

Am J Respir Cell Mol Biol

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Matrix metalloproteinases (MMPs) recently appeared as key regulators of inflammation, allowing recruitment and clearance of inflammatory cells and modifying the biological activity of many peptidic mediators by cleavage. MMP-19 is a newly described MMP and preferentially cleaves matrix proteins such as collagens and tenascin-C. The role of MMP-19 in asthma has not been described to date. The purpose of the present study was to assess MMP-19 expression in a murine asthma model and to address biological effects of MMP-19 deficiency in mice. Allergen- inflammation homeostasis through preventing tenascin protein accumulation.

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Section: Mmp-19 Knock-out (Mmp-19mentioning

confidence: 99%

“…Initially identified as an autoantigen in patients with rheumatoid arthritis (31), MMP-19 is a putative new molecular mediator of inflammation. The recently generated knock-out (KO) mice for MMP-19 (32,33) provide a suitable tool to decipher the potential implication of MMP-19 in allergen-induced asthma.…”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinase-19 Deficiency Promotes Tenascin-C Accumulation and Allergen-Induced Airway Inflammation

Guéders¹,

Hirst²,

Quesada-Calvo³

et al. 2010

Am J Respir Cell Mol Biol

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“…A number of studies using cancer models combined with selective ablation of the candidate gene in mice have thus proven to retard disease progression (Wilson et al, 1997;Itoh et al, 1998;Coussens et al, 2000), while other experiments have demonstrated that MMPs have either a limited role, or in certain instances, confer a protective role in disease progression (Masson et al, 1998;Andarawewa et al, 2003;Balbin et al, 2003;McCawley et al, 2004;Pendas et al, 2004). Collectively, these data demonstrate that the role of MMPs in disease progression is highly diverse and not solely confined to a role in tumor promotion.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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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.

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“…A role of MMP-19 during angiogenesis is suggested by its expression in endothelial cells of synovial capillaries following injury and inflammation (3,25). However, the ex vivo sprouting of endothelial cells from aortic rings was not affected by MMP-19 deficiency (24). Therefore, the contribution of MMP-19 during angiogenic processes remains controversial.…”

Section: Introductionmentioning

confidence: 99%

“…Evidence for MMP-19 involvement in tissue remodeling events, such as those occurring during adipogenesis and tumor progression, have been provided by the recent generation of MMP-19-deficient mice (24). Although lack of MMP-19 did not affect mice viability, fertility, and development, it led to a diet-induced obesity and a decreased susceptibility to skin tumors induced by chemical carcinogens.…”

Section: Introductionmentioning

confidence: 99%

Earlier Onset of Tumoral Angiogenesis in Matrix Metalloproteinase-19–Deficient Mice

et al. 2006

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Among matrix metalloproteinases (MMP), MMP-19 displays unique structural features and tissue distribution. In contrast to most MMPs, MMP-19 is expressed in normal human epidermis and down-regulated during malignant transformation and dedifferentiation. The contribution of MMP-19 during tumor angiogenesis is presently unknown. In an attempt to give new insights into MMP-19 in vivo functions, angiogenic response of mutant mice lacking MMP-19 was analyzed after transplantation of murine malignant PDVA keratinocytes and after injection of Matrigel supplemented with basic fibroblast growth factor. In situ hybridization and immunohistochemical analysis revealed that MMP-19 is produced by host mesenchymal cells but not by endothelial capillary cells or CD11b-positive inflammatory cells. Based on a new computer-assisted method of quantification, we provide evidence that host MMP-19 deficiency was associated with an increased early angiogenic response. In addition, increased tumor invasion was observed in MMP-19À/À mice. We conclude that, in contrast to most MMPs that promote tumor progression, MMP-19 is a negative regulator of early steps of tumor angiogenesis and invasion. These data highlight the requirement to understand the individual functions of each MMP to improve anticancer strategies. (Cancer Res 2006; 66(10): 5234-41)

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Diet-Induced Obesity and Reduced Skin Cancer Susceptibility in Matrix Metalloproteinase 19-Deficient Mice

Cited by 91 publications

References 42 publications

Matrix Metalloproteinase-19 Deficiency Promotes Tenascin-C Accumulation and Allergen-Induced Airway Inflammation

Matrix Metalloproteinase-19 Deficiency Promotes Tenascin-C Accumulation and Allergen-Induced Airway Inflammation

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

Earlier Onset of Tumoral Angiogenesis in Matrix Metalloproteinase-19–Deficient Mice

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