Loss of epidermal MMP-14 expression interferes with angiogenesis but not with re-epithelialization

Zigrino, Paola; Ayachi, Ouissam; Schild, Alexander; Kaltenberg, Jennifer; Zamek, Jan; Nischt, Roswitha; Koch, Manuel; Mauch, Cornelia

doi:10.1016/j.ejcb.2012.05.003

Cited by 34 publications

(19 citation statements)

References 38 publications

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“…Mmp14 KO mice were as described previously ( Zhou et al, 2000 ). To generate mice in which Mmp14 is ablated in tendon-lineage cells, we crossed mice-expressing Cre recombinase under the control of Scleraxis (Scx-Cre; C57BL/6) ( Blitz et al, 2013 ) with mice carrying the floxed exons (exons 2 to 4) of the Mmp14 gene ( Mmp14 lox/lox ; C57BL/6) ( Zigrino et al, 2012 ). Mmp13 KO embryos were a generous gift from Zena Werb ( Stickens et al, 2004 ).…”

Section: Methodsmentioning

confidence: 99%

Matrix metalloproteinase 14 is required for fibrous tissue expansion

Taylor

Yeung

Kalson

et al. 2015

eLife

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Type I collagen-containing fibrils are major structural components of the extracellular matrix of vertebrate tissues, especially tendon, but how they are formed is not fully understood. MMP14 is a potent pericellular collagenase that can cleave type I collagen in vitro. In this study, we show that tendon development is arrested in Scleraxis-Cre::Mmp14 lox/lox mice that are unable to release collagen fibrils from plasma membrane fibripositors. In contrast to its role in collagen turnover in adult tissue, MMP14 promotes embryonic tissue formation by releasing collagen fibrils from the cell surface. Notably, the tendons grow to normal size and collagen fibril release from fibripositors occurs in Col-r/r mice that have a mutated collagen-I that is uncleavable by MMPs. Furthermore, fibronectin (not collagen-I) accumulates in the tendons of Mmp14-null mice. We propose a model for cell-regulated collagen fibril assembly during tendon development in which MMP14 cleaves a molecular bridge tethering collagen fibrils to the plasma membrane of fibripositors.DOI: http://dx.doi.org/10.7554/eLife.09345.001

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Section: Methodsmentioning

confidence: 99%

Matrix metalloproteinase 14 is required for fibrous tissue expansion

Taylor

Yeung

Kalson

et al. 2015

eLife

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“…Of note, additional, “associated” collagen types like collagen XV and XVIII [208] seem to regulate the thickness of the collagen IV mat and thus of BMs. Interestingly, proteolytic fragments of all three collagen types or perlecan restrict angiogenesis especially in cancer [209–216], which may concurrently normalize the tumor microvasculature and reduce vessel leakiness as observed previously when interfering with experimental tumor angiogenesis [172]. Interestingly in this context, laminin-332 has also been detected in tumor vessels and stromal cells like myofibroblasts, thus providing guiding tracks for migrating tumor cells in metastasis or anchorage for cell arrest, respectively, at vessel walls and distant secondary sites [37, 38, 40, 217].…”

Section: Cutaneous Microvasculature Is More Severely Affected By Mmentioning

confidence: 99%

Skin Basement Membrane: The Foundation of Epidermal Integrity—BM Functions and Diverse Roles of Bridging Molecules Nidogen and Perlecan

Breitkreutz

Koxholt

Thiemann

et al. 2013

BioMed Research International

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The epidermis functions in skin as first defense line or barrier against environmental impacts, resting on extracellular matrix (ECM) of the dermis underneath. Both compartments are connected by the basement membrane (BM), composed of a set of distinct glycoproteins and proteoglycans. Herein we are reviewing molecular aspects of BM structure, composition, and function regarding not only (i) the dermoepidermal interface but also (ii) the resident microvasculature, primarily focusing on the per se nonscaffold forming components perlecan and nidogen-1 and nidogen-2. Depletion or functional deficiencies of any BM component are lethal at some stage of development or around birth, though BM defects vary between organs and tissues. Lethality problems were overcome by developmental stage- and skin-specific gene targeting or by cell grafting and organotypic (3D) cocultures of normal or defective cells, which allows recapitulating BM formation de novo. Thus, evidence is accumulating that BM assembly and turnover rely on mechanical properties and composition of the adjacent ECM and the dynamics of molecular assembly, including further “minor” local components, nidogens largely functioning as catalysts or molecular adaptors and perlecan as bridging stabilizer. Collectively, orchestration of BM assembly, remodeling, and the role of individual players herein are determined by the developmental, tissue-specific, or functional context.

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“…Membranes were blocked for 1 h with 5% milk powder and incubated overnight at 4 °C with the primary antibody. Primary antibodies used were anti-ADAM9, anti-decorin, (AF949 and MAB143, respectively, all from R&D Systems, Wiesbaden, Germany), anti-collagen type I (1:500; 20315035505 from Quartett, Berlin, Germany), anti-fibronectin and anti-actin (F3648 and A2668, both 1:1000; from Sigma Aldrich, Diesenhofen, Germany), and anti-MMP-13 (sc-30073, from Santa Cruz, Heidelberg, Germany; 1:1000), anti-MMP-14 (1:500) [ 18 ]. After washing, membranes were incubated with HRP-labeled secondary antibody (from Dako, Hamburg, Germany) for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Loss of ADAM9 Leads to Modifications of the Extracellular Matrix Modulating Tumor Growth

et al. 2020

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ADAM9 is a metalloproteinase strongly expressed at the tumor-stroma border by both tumor and stromal cells. We previously showed that the host deletion of ADAM9 leads to enhanced growth of grafted B16F1 melanoma cells by a mechanism mediated by TIMP1 and the TNF-α/sTNFR1 pathway. This study aimed to dissect the structural modifications in the tumor microenvironment due to the stromal expression of ADAM9 during melanoma progression. We performed proteomic analysis of peritumoral areas of ADAM9 deleted mice and identified the altered expression of several matrix proteins. These include decorin, collagen type XIV, fibronectin, and collagen type I. Analysis of these matrices in the matrix producing cells of the dermis, fibroblasts, showed that ADAM9−/− and wild type fibroblasts synthesize and secreted almost comparable amounts of decorin. Conversely, collagen type I expression was moderately, but not significantly, decreased at the transcriptional level, and the protein increased in ADAM9−/− fibroblast mono- and co-cultures with melanoma media. We show here for the first time that ADAM9 can release a collagen fragment. Still, it is not able to degrade collagen type I. However, the deletion of ADAM9 in fibroblasts resulted in reduced MMP-13 and -14 expression that may account for the reduced processing of collagen type I. Altogether, the data show that the ablation of ADAM9 in the host leads to the altered expression of peritumoral extracellular matrix proteins that generate a more favorable environment for melanoma cell growth. These data underscore the suppressive role of stromal expression of ADAM9 in tumor growth and call for a better understanding of how protease activities function in a cellular context for improved targeting.

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Loss of epidermal MMP-14 expression interferes with angiogenesis but not with re-epithelialization

Cited by 34 publications

References 38 publications

Matrix metalloproteinase 14 is required for fibrous tissue expansion

Matrix metalloproteinase 14 is required for fibrous tissue expansion

Skin Basement Membrane: The Foundation of Epidermal Integrity—BM Functions and Diverse Roles of Bridging Molecules Nidogen and Perlecan

Loss of ADAM9 Leads to Modifications of the Extracellular Matrix Modulating Tumor Growth

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