Matrix metalloproteinase 11 (MMP‐11; stromelysin‐3) and synthetic inhibitors

Matziari, Magdalini; Dive, Vincent; Yiotakis, Athanasios

doi:10.1002/med.20066

Cited by 53 publications

(35 citation statements)

References 85 publications

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“…MMP-11 is expressed in fibroblasts and was originally identified as a stromal-derived factor upregulated in breast cancer (Basset et al 1990). However, MMP-11 is not able to degrade any of the major extracellular matrix components, including collagens, and its biological substrate and function are unknown (Matziari et al 2007). Thus, it is an intriguing finding, but of unclear significance at this point.…”

Section: Resultsmentioning

confidence: 99%

uPARAP expression during murine lung development

Smith¹,

Wagner²,

Huizar³

et al. 2008

Gene Expression Patterns

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Lung remodeling requires active collagen deposition and degradation. Urokinase plasminogen activator receptor-associated protein (uPARAP), or Endo 180, is a cell surface receptor for collagens, which leads to collagen internalization and degradation. Thus, uPARAP-mediated collagen degradation is an additional pathway for matrix remodeling in addition to matrix remodeling mediated by matrix metalloproteinases and cathepsins. Using immunohistochemistry, we demonstrate extensive uPARAP expression in the mesenchyme throughout murine lung development. By immunofluorescence, we demonstrate significant overlap of uPARAP expression with collagen IV expression, but minimal overlap with collagen I expression in the developing murine lung. Finally, we compared lung development between wild-type and uPARAP −/− mice, and found no significant histologic differences, indicating the presence of alternative collagen degradation pathways during murine lung development.Keywords lung development; collagen; uPARAP; Endo 180 Results and DiscussionUrokinase plasminogen activator receptor-associated protein (uPARAP), or Endo180, is a newly described cell-surface receptor that binds and internalizes collagens, including types I, IV, and V, targeting them for lysosomal degradation (Behrendt et al. 2000;Engelholm et al. 2003;Engelholm et al. 2001;Kjoller et al. 2004). A member of the mannose receptor family, uPARAP is expressed on macrophages and mesenchymal cells, including chondrocytes and some fibroblasts (Howard et al. 2004;Sheikh et al. 2000). Mesenchymal cells that lack uPARAP are unable to internalize collagen (Curino et al. 2005;East et al. 2003;Engelholm et al. 2003;Kjoller et al. 2004;Madsen et al. 2007;Mousavi et al. 2005). In addition to its role in collagen internalization and degradation, uPARAP contributes to the adhesion and migration of collagen in vitro (Engelholm et al. 2003). uPARAP may also play a role in human gingival re-epithelialization and remodeling after injury (Honardoust et al. 2006). In addition, uPARAP is expressed in tumor stromal cells and has a role in tumor progression (Curino et al. 2005;Sulek et al. 2007). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. During lung development, the matrix undergoes active remodeling during the formation and differentiation of airways, vasculature, and mature alveoli. In particular, during the saccular stage (E17.5 to post-natal day 5 (PN5)) and alveolar stage (PN5-PN30), the lung interstitium undergoes extensive remodeling with a decrease in the interstitial space, maturation and narrowing of the blood-air barrier and t...

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Section: Resultsmentioning

confidence: 99%

uPARAP expression during murine lung development

Smith¹,

Wagner²,

Huizar³

et al. 2008

Gene Expression Patterns

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“…Despite the identification of possible in vitro substrates for MMP-11 (Matziari et al, 2007), there is lack of convincing evidences that support their in vivo cleavage (see Table 3). Identification of the in vivo physiological substrates of MMP-11, as well as the development of potent and specific inhibitors for this particular MMP family member would certainly provide valuable information about the physio-pathological roles of MMP-11.…”

Section: Structural Peculiarities and Biological Aspectsmentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

208

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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“…In fact, the CSGs FGFR4, CDK4 , and several MMPs , which are specifically overexpressed in rhabdomyosarcoma ( FGFR4 ), liposarcoma ( CDK4 ), and desmoid tumors, leiomyoma, osteosarcoma and adamantinomatous craniopharyngioma ( MMPs ) (Supplementary Table 5), respectively, could be targeted by specific inhibitors currently in clinical trials. 43–45 …”

Section: Discussionmentioning

confidence: 99%

Systematic identification of cancer-specific MHC-binding peptides with RAVEN

Baldauf¹,

Gerke²,

Kirschner

et al. 2018

OncoImmunology

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Immunotherapy can revolutionize anti-cancer therapy if specific targets are available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo-antigens generated by protein-coding missense mutations. Here, we describe an algorithm and user-friendly software named RAVEN (Rich Analysis of Variable gene Expressions in Numerous tissues) that automatizes the systematic and fast identification of CSG-encoded peptides highly affine to Major Histocompatibility Complexes (MHC) starting from transcriptome data. We applied RAVEN to a dataset assembled from 2,678 simultaneously normalized gene expression microarrays comprising 50 tumor entities, with a focus on oligo-mutated pediatric cancers, and 71 normal tissue types. RAVEN performed a transcriptome-wide scan in each cancer entity for gender-specific CSGs, and identified several established CSGs, but also many novel candidates potentially suitable for targeting multiple cancer types. The specific expression of the most promising CSGs was validated in cancer cell lines and in a comprehensive tissue-microarray. Subsequently, RAVEN identified likely immunogenic CSG-encoded peptides by predicting their affinity to MHCs and excluded sequence identity to abundantly expressed proteins by interrogating the UniProt protein-database. The predicted affinity of selected peptides was validated in T2-cell peptide-binding assays in which many showed binding-kinetics like a very immunogenic influenza control peptide. Collectively, we provide an exquisitely curated catalogue of cancer-specific and highly MHC-affine peptides across 50 cancer types, and a freely available software (https://github.com/JSGerke/RAVENsoftware) to easily apply our algorithm to any gene expression dataset. We anticipate that our peptide libraries and software constitute a rich resource to advance anti-cancer immunotherapy.

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Matrix metalloproteinase 11 (MMP‐11; stromelysin‐3) and synthetic inhibitors

Cited by 53 publications

References 85 publications

uPARAP expression during murine lung development

uPARAP expression during murine lung development

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Systematic identification of cancer-specific MHC-binding peptides with RAVEN

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