Disease relevance of ECM1

• ECM1 protein is a seminal plasma biomarker for differentiation between obstructive (OA) and non-obstructive (NOA) azoospermia [1], [2].
• Extracellular matrix protein 1 (ECM1) is over-expressed in malignant epithelial tumors [3].
• In the present study, we used immunohistochemical staining to examine the expression of ECM1 in a panel of human tumors and found that it was closely correlated with some types of tumors including: invasive breast ductal carcinoma (83%), esophageal squamous carcinoma (73%), gastric cancer (88%) and colorectal cancer (78%) [3].
• We hypothesized that altered extracellular matrix (ECM) turnover contributes to the pathophysiology of cardiac disease in AFD [4].
• Extracellular matrix turnover and disease severity in Anderson-Fabry disease [4].
• CONCLUSIONS: The ECM protein PG-I inhibits growth by arresting pancreatic cancer cells in G1 and may be part of a host defense mechanism aimed at slowing down pancreatic tumor progression [5].
• We identified three surrogate markers of ECM1 tumours: MARCO, PUNC, and SPARC, whose expression levels were associated with breast cancer survival and risk of recurrence [6].

Psychiatry related information on ECM1

• The angiopathy of subcortical arteriosclerotic encephalopathy (Binswanger's disease): immunohistochemical studies using markers for components of extracellular matrix, smooth muscle actin and endothelial cells [7].
• The ECM turnover is influenced by physical activity, and both collagen synthesis and degrading metalloprotease enzymes increase with mechanical loading [8].
• Proteolysis on the cell surface and in the extracellular matrix is essential for normal cellular functions during development and in the adult, but it may also have undesirable consequences, such as promoting cancer, arthritis, and Alzheimer's disease [9].
• Signals from dynamic cellular interactions between the extracellular matrix and neighboring cells ultimately input into the cellular decision-making process [10].
• The superfamily of proteins with von Willebrand factor type A-like domains: one theme common to components of extracellular matrix, hemostasis, cellular adhesion, and defense mechanisms [11].

High impact information on ECM1

• In addition, PTX3 is essential in female fertility because it acts as a nodal point for the assembly of the cumulus oophorus hyaluronan-rich extracellular matrix [12].
• Within these sites, integrins facilitate cell movement via interactions with the extracellular matrix, and promote and stabilize antigen-specific interactions between T lymphocytes and APCs that are critical for initiating T cell-activation events [13].
• Critical determinants of the in vivo activities of chemokines in the immune system include their presentation by endothelial cells and extracellular matrix molecules, as well as their cellular uptake via "silent" chemokine receptors (interceptors) leading either to their transcytosis or to degradation [14].
• Finally, IL-13 was revealed as a potent mediator of tissue fibrosis in both schistosomiasis and asthma, which indicates that it is a key regulator of the extracellular matrix [15].
• Cycles of avidity change are also observed for other T lymphocyte integrins which bind to extracellular matrix components [16].

Chemical compound and disease context of ECM1

• BACKGROUND: Matrix metalloproteinases (MMPs) digest extracellular matrix proteins and may play a role in the pathogenesis of bronchial asthma [17].
• ABSTRACT : BACKGROUND : Urokinase-type Plasminogen Activator (uPA), a serine protease, plays a pivotal role in human breast cancer metastasis by mediating the degradation of extracellular matrix proteins and promoting cell motility [18].
• Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients' sera [19].
• Matrix metalloproteinases (MMP) constitute a large group of Zn(2+) dependent endopeptidases with the ability to degrade extracellular matrix and are possibly responsible for the development of tissue edema in chronic sinusitis [20].
• Immunohistochemical expression of cathepsin D in correlation with extracellular matrix component, steroid receptor status and proliferative indices in breast cancer [21].

Biological context of ECM1

• Using a candidate gene approach (comparison of control versus LP gene expression in cultured fibroblasts) and subsequent direct sequencing of genomic DNA, we identified six different homozygous loss-of-function mutations in the extracellular matrix protein 1 gene (ECM1) [22].
• Although the precise function of ECM1 is not known, our findings provide the first clinical indication of its relevance to skin adhesion, epidermal differentiation, wound healing, scarring, angiogenesis/angiopathy and basement membrane physiology, as well as defining the molecular basis of this inherited disorder [22].
• Taken with the previously documented mutations in ECM1, this study supports the view that exons 6 and 7 are the most common sites for ECM1 mutations in lipoid proteinosis [23].
• The mutation 507delT occurred in two unrelated subjects on different ECM1 haplotypes and may therefore represent a recurrent mutation in lipoid proteinosis [23].
• The ECM1 gene maps at chromosome 1q21 outside the epidermal differentiation complex region [24].

Anatomical context of ECM1

• The ECM1 gene appears to be expressed as a 1.8-kb transcript predominantly in placenta and heart, while an additional 1.4-kb alternatively spliced message was detected in tonsils [24].
• RESULTS: PG-I was overexpressed in the ECM of pancreatic cancer samples compared with normal pancreas or chronic pancreatitis tissues [5].
• Distribution of hyaluronan during extracellular matrix remodeling in human restenotic arteries and balloon-injured rat carotid arteries [25].
• CONCLUSION: These data suggest that OSM promotes angiogenesis and endothelial cell migration and potentiates the effects of IL-1beta in promoting extracellular matrix turnover and human cartilage degradation [26].
• The chromosomal localization and the Ecm1b expression in skin prompted us to investigate the role of Ecm1 in keratinocyte differentiation [27].

Associations of ECM1 with chemical compounds

• The autosomal recessive disorder lipoid proteinosis results from mutations in extracellular matrix protein 1 (ECM1), a glycoprotein expressed in several tissues (including skin) and composed of two alternatively spliced isoforms, ECM1a and ECM1b, the latter lacking exon 7 of this 10-exon gene (ECM1) [23].
• The relationship of VEGF and PGE2 expression to extracellular matrix remodelling of the tenosynovium in the carpal tunnel syndrome [28].
• Decorin is a small leucine-rich extracellular matrix proteoglycan composed of a core protein with a single glycosaminoglycan (GAG) chain near the N-terminus and N-glycosylated at three potential sites [29].
• Cell proliferation is dependent upon the activation of receptor tyrosine kinases and integrins by soluble growth factors and extracellular matrix proteins, respectively [30].
• We have examined the possibility that the fate of stellate cells is influenced by the extracellular matrix through the intermediary of alpha(v)beta(3) integrin. alpha(v)beta(3) integrin was expressed by activated, myofibroblastic rat and human stellate cells in culture [31].

Physical interactions of ECM1

• Among the adhesion molecules, the integrins of the beta 1-subfamily are known to direct cell-cell and cell-matrix interactions and evidence has been provided that CD34-positive stem cells bind either to the bone marrow stroma or to the extracellular matrix proteins through the beta 1-integrins [32].
• This posttranslational modification was required for CD44-mediated binding to the extracellular matrix component hyaluronan and to vascular endothelial cells [33].
• The latent TGF-beta binding proteins (LTBPs-1, -2 and -3) mediate the secretion and, subsequently, the association of latent TGF-beta complexes with the extracellular matrix (ECM) [34].
• VEGF145, a secreted vascular endothelial growth factor isoform that binds to extracellular matrix [35].
• Estradiol stimulates the proliferation of estrogen-receptor(ER)-positive ovarian-cancer cells, as well as expression of fibulin-1, a fibronectin-binding extracellular matrix protein [36].

Enzymatic interactions of ECM1

• MT1-MMP hydrolyzes a variety of extracellular matrix components and is a physiological activator of pro-MMP-2, another MMP involved in malignancy [37].
• Focal adhesion kinase (FAK) becomes activated and tyrosine-phosphorylated in response to cell adhesion to extracellular matrix proteins in a variety of cell types, and associates with a number of signaling molecules, structural proteins, and beta integrin cytoplasmic domains [38].
• Bone morphogenetic protein (BMP)-1 is a zinc-dependent metalloproteinase that cleaves a variety of extracellular matrix substrates, including type I procollagen [39].
• ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage [40].
• Endometase may selectively cleave extracellular matrix proteins, inactivate serpins, and process cytokines [41].

Co-localisations of ECM1

• Fibronectin is a prominent adhesive molecule of the extracellular matrix that is often co-localized with tenascin-C in these processes [42].
• The exogenous fibronectin co-localized in the extracellular matrix with endogenous cell-derived fibronectin, and its deposition into the matrix was inhibited by blocking antibodies against the beta1 integrin receptor [43].
• Osteocytes make contact with the extracellular matrix via small attachment points which colocalize with vinculin [44].

Regulatory relationships of ECM1

• This mutation, which leads to a nonsynonymous amino-acid change within the active site of the enzyme may reduce MMP-9-induced degradation of the structural components of the ECM during inflammatory episodes in trachoma and its associated fibrosis [45].
• In this study, we examined the role of CTGF as a downstream mediator of TGF-beta1-induced ECM production and cell growth in osteoblasts [46].
• Cell cycle progression in mammalian cells is strictly regulated by both integrin-mediated adhesion to the extracellular matrix and by binding of growth factors to their receptors [47].
• Because ligation of CD44 by hyaluronic acid can induce epithelial cell movement on extracellular matrix, we investigated whether molecular mimicry by the GAS hyaluronic acid capsule might induce similar cellular responses [48].
• ICAM-3 regulates lymphocyte morphology and integrin-mediated T cell interaction with endothelial cell and extracellular matrix ligands [49].

Other interactions of ECM1

• The increased expression of TIMP-1 may reflect a specific temporal inhibition of collagenolysis and thereby a time-dependent regulation of ECM breakdown in areas surrounding the apex of the follicle [50].
• Matrix metalloproteinases (MMPs) and urokinase plasminogen activation (uPA) system are shown to be involved in tumor invasion as they help in degradation of extracellular matrix (ECM) proteins and thus assist in the movement of cells [51].
• Taken together, this study discusses MMP-9 inhibition potential of CCOS and their involvement to demote degradation and cellular invasion of extracellular matrix (ECM) and basement membrane [52].
• These results suggest that PTEN inhibits glioma cell invasion in two ways: suppressing proteolysis of the extracellular matrix by MMPs and modulating the migratory activity of glioma cells to a less motile nature by inactivating two Rho-family GTP-binding proteins, Rac and Cdc42 [53].
• In squamous cell carcinomas of the head and neck (SCCHN), hypoxia is considered a pivotal physiological modulator for malignant progression, whereby the plasminogen activation system is involved in overlapping functions such as the shaping of the extracellular matrix, cell proliferation and signal transduction [54].

Analytical, diagnostic and therapeutic context of ECM1

• We now report the radiation hybrid mapping of human ECM1 to 1q21, and the gene structure and coding sequence of human ECM1 [55].
• Analysis of human skeletal muscle after 48 h immobilization reveals alterations in mRNA and protein for extracellular matrix components [56].
• We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease [19].
• Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1 [19].
• This was initially suggested by in situ hybridization studies of mouse embryos indicating that the ECM1 message was associated with blood vessels and its expression pattern was similar to that of flk-1, a recognized marker for endothelium [57].

References