Activity of Matrix Metalloproteinases-2 and -9 in Advanced Laryngeal Cancer

2003 ◽  
Vol 128 (1) ◽  
pp. 132-136 ◽  
Author(s):  
Michal Bogusiewicz ◽  
Marta Stryjecka-Zimmer ◽  
Marcin Szymanski ◽  
Tomasz Rechberger ◽  
Wieslaw Golabek
Keyword(s):  
Matrix Metalloproteinases ◽  
Laryngeal Cancer ◽  
Malignant Tumors ◽  
Proteolytic Enzymes ◽  
Distant Metastases ◽  
Normal Mucosa ◽  
Collagen Type Iv ◽  
Primary Therapy ◽  
Tissue Samples ◽  
Type Iv

OBJECTIVES: Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) are proteolytic enzymes that digest collagen type IV and other components of the basement membrane. They play a key role in local invasion and the formation of distant metastases by malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and MMP-9 in stage III and IV laryngeal cancers. STUDY DESIGN: In the study we used specimens of laryngeal cancer and surrounding normal mucosa obtained from 23 patients undergoing surgical treatment as a primary therapy. After extraction of MMP-2 and MMP-9 from tissue samples, their activity was assessed with zymography. RESULTS: Greater activity of MMP-2 and MMP-9 and a higher active/latent MMP-2 ratio were found in cancer compared with normal mucosa. Moreover, N2 tumors revealed greater activity of MMP-2 in comparison with N1 and N0 tumors. CONCLUSIONS: Results of the study indicate that both MMP-2 and MMP-9 may be involved in the expansion of laryngeal cancer. MMP-2 may also play an important role in the lymphatic spread of some laryngeal tumors.

scholarly journals Type IV collagen immunoreactivity of basement membrane in inflammatory-regenerative and dysplastic lesions of the flat colonic mucosa

2003 ◽  
Vol 3 (1) ◽  
pp. 30-35
Author(s):  
Svjetlana Radović ◽  
Ivan Selak ◽  
Mirsad Babić ◽  
Željka Knežević ◽  
Zora Vukobrat-Bijedić
Keyword(s):  
Basement Membrane ◽  
Colon Adenocarcinoma ◽  
Normal Mucosa ◽  
Collagen Iv ◽  
Epithelial Dysplasia ◽  
Collagen Type Iv ◽  
Severe Dysplasia ◽  
Colon Mucosa ◽  
Mild Dysplasia ◽  
Type Iv

The aim of this research is to establish by immunohistochemistry if there is a change in the expression of collagen type IV, as a substitute of basement membrane, in development of epithelial dysplasia in chronically inflamed colon mucosa.Methods. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions. There were 108 cases of mild dysplasia, 58 cases of moderate and 30 cases severe dysplasia, respectively. Visualisation of collagen IV and its way of expression within basement membrane of glandular crypts was performed by immunohistochemistry and then compared with findings in normal colon mucosa and colon adenocarcinoma tissue.Results. Changes in the expression of collagen IV comprised of its focal irregularities, diffuse thinning and/or thickening, focal interruptions or its complete absence. Significant changes in the expression of collagen IV in relation to normal mucosa already occur in inflammatory-regenerative mucosa. In mild dysplasia, these changes are more intensive in relation to those in inflammatory altered mucosa as well as at severe dysplasia in relation to moderate dysplasia. Changes in the expression of collagen IV in severe dysplasia are significantly more serious than in moderate dysplasia but are identical to those in colon adenocarcinoma tissue.Conclusion. These findings suggest that change in the expression of collagen IV is in correlation to a degree of epithelial dysplasia that developed in flat chronically inflamed colon mucosa.

scholarly journals Matrix metalloproteinases in the process of invasion and metastasis of breast cancer

2006 ◽  
Vol 14 (3-4) ◽  
pp. 136-140 ◽  
Author(s):  
Gordana Konjevic ◽  
Sandra Stankovic
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinases ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Proteolytic Enzymes ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Collagen Type Iv ◽  
Cell Contact ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition

Metastatic cascade in malignant tumors, including breast cancer, starts with localized invasion of the host tissue. This process, requiring that tumor cells separate from each other, includes loss of homotypic and heterotypic cell adhesion and cell-cell contact inhibition, acquisition of motility, exacerbated by "epithelial-to-mesenchymal transition", and production of proteolytic enzymes which degrade basal membrane and extracellular matrix. In this sense, aside from urokinase type plasminogen activator, increased expression and activity of matrix metalloproteinases (MMPs) is one of the earliest and most sustained events in tumor progression, playing a role in angiogenesis, invasion and metastasis. MMPs are a family of 23 zinc metalloproteinases, secreted as latent pro-enzymes, activated by proteolytic cleavage, and inhibited by the tissue inhibitors of metalloproteinases. The most commonly connected MMPs with the processes of metastasis are MMP-2 (gelatinase A) and MMP-9 (gelatinase B), due to their ability to degrade collagen type IV, major component of vascular basement membrane. MMP-2 and MMP-9 are also required for the switch to the "angiogenic phenotype" during tumor progression and activation of dormant tumor cells. The association of the increase in serum MMP-2 and MMP-9 activity and clinical stage suggests the usefulness of these parameters as markers in the follow-up and prognosis of breast cancer patients. The concept of "stromal-directed therapy" of cancer, with MMP-inhibitors directed against MMPs as targets, is based on the observed MMP up-regulation in tumors.

scholarly journals The Clinicopathological Significance of miR-133a in Colorectal Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Timothy Ming-Hun Wan ◽  
Colin Siu-Chi Lam ◽  
Lui Ng ◽  
Ariel Ka-Man Chow ◽  
Sunny Kit-Man Wong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Negative Correlation ◽  
Target Genes ◽  
Distant Metastases ◽  
Normal Mucosa ◽  
Tnm Staging ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Endogenous Expression ◽  
Clinicopathological Significance

This study determined the expression of microRNA-133a (MiR-133a) in colorectal cancer (CRC) and adjacent normal mucosa samples and evaluated its clinicopathological role in CRC. The expression of miR-133a in 125 pairs of tissue samples was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and correlated with patient’s clinicopathological data by statistical analysis. Endogenous expression levels of several potential target genes were determined by qRT-PCR and correlated using Pearson’s method. MiR-133a was downregulated in 83.2% of tumors compared to normal mucosal tissue. Higher miR-133a expression in tumor tissues was associated with development of distant metastasis, advanced Dukes and TNM staging, and poor survival. The unfavorable prognosis of higher miR-133a expression was accompanied by dysregulation of potential miR-133a target genes, LIM and SH3 domain protein 1 (LASP1), Caveolin-1 (CAV1), and Fascin-1 (FSCN1). LASP1 was found to possess a negative correlation (γ=-), whereas CAV1 exhibited a significant positive correlation (γ=), and a stronger correlation was found in patients who developed distant metastases (γ=). In addition, a negative correlation of FSCN1 was only found in nonmetastatic patients. In conclusion, miR-133a was downregulated in CRC tissues, but its higher expression correlated with adverse clinical characteristics and poor prognosis.

Involvement of lung interstitial proteoglycans in development of hydraulic- and elastase-induced edema

1998 ◽  
Vol 275 (3) ◽  
pp. L631-L635 ◽  
Author(s):  
Alberto Passi ◽  
Daniela Negrini ◽  
Riccardo Albertini ◽  
Giancarlo De Luca ◽  
Giuseppe Miserocchi
Keyword(s):  
Basement Membrane ◽  
Gel Filtration ◽  
Weight Ratio ◽  
Dry Weight ◽  
Collagen Type Iv ◽  
Tissue Samples ◽  
Type Iv ◽  
Saline Loading ◽  
Intravenous Saline ◽  
Wet Weight

We extracted and isolated proteoglycans from lung tissue samples obtained from three groups of anesthetized rabbits: 1) control animals (C; n= 8) killed by overdose after 180 min; 2) animals receiving an intravenous saline infusion (S; n = 4, 1.5 ml ⋅ kg-1 ⋅ min-1) for 180 min; 3) animals receiving an intravenous bolus of 200 μg of pancreatic elastase (E; n = 4), killed after 200 min. The lung dry weight-to-wet weight ratio in the three groups was 5.2 ± 0.2, 6.0 ± 0.4, and 5.6 ± 0.5, respectively. Gel-filtration analysis showed a massive fragmentation of the versican family of the extracellular matrix (ECM) in the S groups and a marked degradation of heparan sulfate-containing proteoglycans, including perlecan of the basement membrane, in the E group. The binding properties of total proteoglycans to other ECM components were lowered in both groups relative to control. The decrease in proteoglycan binding was more pronounced for collagen type IV in the E group relative to C (−93.5%, P < 0.05) and for hyaluronic acid in the S groups (−85.8%, P < 0.05). These findings suggest that elastase treatment produces a major degree of damage to the organization of basement membrane, whereas saline loading affects more markedly the architecture of interstitial ECM. Qualitative zymography performed on lung extracts showed increased gelatinase activities in both S and E groups, providing direct evidence that the activation of tissue proteinases may play a role in acute lung injury.

scholarly journals Differential Notch and TGFβ Signaling in Primary Colorectal Tumors and Their Corresponding Metastases

2008 ◽  
Vol 30 (1) ◽  
pp. 1-11
Author(s):  
Liesbeth M. Veenendaal ◽  
Onno Kranenburg ◽  
Niels Smakman ◽  
Annemarie Klomp ◽  
Inne H. M. Borel Rinkes ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Lung Metastases ◽  
Tumor Development ◽  
Distant Metastases ◽  
Normal Mucosa ◽  
Normal Colonic Mucosa ◽  
Colorectal Tumors ◽  
Vimentin Expression ◽  
Aberrant Expression ◽  
Tissue Samples

Background: Loss of epithelial morphology and the acquisition of mesenchymal characteristics may contribute to metastasis formation during colorectal tumorigenesis. The Wnt, Notch and TGFβ signaling pathways control tissue homeostasis and tumor development in the gut. The relationship between the activity of these pathways and the expression of epithelial and mesenchymal markers was investigated in a series of primary colorectal tumors and their corresponding metastases.Methods: Tissue samples of primary colorectal tumors, normal colonic mucosa, and regional and systemic metastases were processed for immunohistochemistry in a tissue microarray format. The expression of mesenchymal (vimentin, fibronectin) and epithelial (E-cadherin) markers was related to markers of Wnt (β-catenin), Notch (HES1) and TGFβ (phospho-SMAD2) signalling. In addition, the KRAS mutation status was assessed.Results: When compared to normal mucosa, primary colorectal tumors showed a marked increase in the levels of cytoplasmic vimentin and nuclear β-catenin, phospho-SMAD2 and HES1. Increased vimentin expression correlated with the presence of oncogenic KRAS and with nuclear β-catenin. The corresponding liver, lymph node, brain and lung metastases did not express vimentin and displayed significantly lower levels of nuclear phospho-SMAD2 and HES1, while retaining nuclear β-catenin.Conclusions: Primary colorectal carcinomas display aberrant expression of vimentin, and have activated Notch and TGFβ signaling pathways. Surprisingly, many regional and distant metastases have lost nuclear HES1 and pSMAD2, suggesting that the activity of the Notch and TGFβ pathways is reduced in secondary colorectal tumors.

Matrix metalloproteinases in urinary system tumors. Part II - Matrix metalloproteinases in urinary bladder carcinoma

2017 ◽  
Vol 7 (1) ◽  
pp. 0-0
Author(s):  
G. Młynarczyk ◽  
J. Kudelski ◽  
B. Darewicz ◽  
Z. Galewska ◽  
L. Romanowicz
Keyword(s):  
Matrix Metalloproteinases ◽  
Urinary Bladder ◽  
Proteolytic Enzymes ◽  
Distant Metastases ◽  
System Structure ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Urinary Bladder Carcinoma ◽  
Urinary System ◽  
Neoplastic Processes ◽  
And Function

Matrix metalloproteinases (MMPs), also referred to as matrixines, provide a group of proteolytic enzymes. They belong to the family of endopeptidases that break down elements of the extracellular matrix, resulting in its continuous remodeling. Their activity is regulated at multiple levels, while tissue inhibitors of metalloproteinases play a major role in this process. Metalloproteinases play a significant part in neoplastic processes due to their contribution to local tumor invasion, the formation of distant metastases, as well as to angiogenesis Urinary tract tumors pose a significant diagnostic and therapeutic challenge and their incidence tends to grow every year. The aim of this second part of the review is to describe the urinary system structure and function, and to highlight the contribution of matrix metalloproteinases to the development of urinary bladder tumors

Matrix metalloproteinases in urinary system tumours. Part I - Matrix metalloproteinases in renal cell carcinoma

2017 ◽  
Vol 7 (1) ◽  
pp. 0-0
Author(s):  
G. Młynarczyk ◽  
J. Kudelski ◽  
B. Darewicz ◽  
Z. Galewska ◽  
L. Romanowicz
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Cell Carcinoma ◽  
Proteolytic Enzymes ◽  
Distant Metastases ◽  
Renal Clear Cell Carcinoma ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Neoplastic Processes ◽  
The Family ◽  
Local Tumour

Extracellular matrix metalloproteinases - MMPs, also referred to as matrixines, provide a group of proteolytic enzymes. They belong to the family of endopeptidases that break down elements of extracellular matrix, resulting in its continuous remodelling. Their activity is regulated at multiple levels, while tissue inhibitors of metalloproteinases play a major role in this process. Metalloproteinases play a significant part in neoplastic processes due to their contribution to local tumour invasion and formation of distant metastases, as well as to angiogenesis Urinary tract tumours pose a significant diagnostic and therapeutic challenge and their incidence tends to grow every year. The aim of this part of review is to describe extracellular matrix and matrix metalloproteinases and to highlight the contribution of matrix metalloproteinases in the development of renal clear cell carcinoma.

scholarly journals Protease treatment combined with immunohistochemistry reveals heterogeneity of normal and neoplastic basement membranes.

1988 ◽  
Vol 36 (2) ◽  
pp. 213-220 ◽  
Author(s):  
F J Leu ◽  
I Damjanov
Keyword(s):  
Smooth Muscle ◽  
Collagen Type ◽  
Malignant Tumors ◽  
Differential Susceptibility ◽  
Basement Membranes ◽  
Benign Tumors ◽  
Collagen Type Iv ◽  
Human Tissues ◽  
Proteolytic Digestion ◽  
Type Iv

Heterogeneity of normal tissue and neoplastic basement membranes was investigated immunohistochemically with monoclonal antibodies and polyclonal antisera to laminin and collagen type IV. Cryostat sections of normal and neoplastic human tissues were digested with bacterial protease or trypsin. The duration of digestion and the concentration of enzyme were varied to determine whether laminin and collagen type IV could be removed differentially from basement membranes from distinct anatomic sites. After digestion, the residual antigenicity of glycoprotein was assessed immunohistochemically. Laminin could be removed more easily from all tissues than could collagen IV, and also much more easily from malignant tumors than from benign tumors or normal tissues. On the basis of susceptibility to proteolytic digestion, basement membranes from normal human tissues were classified as susceptible (e.g., heart and smooth muscle of gastrointestinal tract and uterus), moderately resistant (e.g., nerve, skeletal muscle, epithelial basement membrane of skin, smooth muscle of arteries), and very resistant (e.g., glomerulus). Differential susceptibility to proteolytic digestion most likely reflects quantitative and possibly also qualitative differences in the composition of basement membranes.

scholarly journals MOLECULAR DIAGNOSIS OF FIBROSIS IN DIFFUSE LIVER DISEASES

2019 ◽  
Vol 22 (2) ◽  
pp. 106-115
Author(s):  
Andrey P. Fisenko ◽  
I. E. Smirnov
Keyword(s):  
Matrix Metalloproteinases ◽  
Liver Diseases ◽  
Transforming Growth Factor ◽  
Clinical Manifestations ◽  
Diagnostic Value ◽  
Collagen Type Iv ◽  
Morphological Examination ◽  
Important Place ◽  
Non Invasive ◽  
Type Iv

Chronic liver diseases (CLD) held an important place in the structure of pediatric hepatology including viral and autoimmune hepatitis, various forms of liver pathology caused by metabolic disorders. They are characterized by a variety of clinical manifestations, a progressive course with the formation of fibrosis and the possibility of its outcome in liver cirrhosis (LC). Liver puncture biopsy with morphological examination of its tissue is the leading method for determining the stage of liver fibrosis (LF) in CLD children. However, it is not always safe for the patient. Using non-invasive imaging methods, it is impossible to detect intermediate stages of fibrosis and it is not always possible to detect signs of CL. Therefore, non-invasive markers of LF, based on the identification of various molecular compounds involved in the formation of components of the extracellular matrix (ECM) or acting as activators of fibrogenesis, are necessary. Hyaluronic acid, collagen type IV, matrix metalloproteinases-2 and -9, a tissue inhibitor of matrix metalloproteinases-1, transforming growth factor beta1, showing diagnostic value for non-invasive monitoring of the development of LF, are well studied among them.

The use of 1nm silver enhanced gold probes for the detection of skin antigens

1990 ◽  
Vol 48 (3) ◽  
pp. 902-903
Author(s):  
J.P Cassella ◽  
H. Shimizu ◽  
A. Ishida-Yamamoto ◽  
R.A.J. Eady
Keyword(s):  
Type Iv Collagen ◽  
Freeze Substitution ◽  
Collagen Type Iv ◽  
Electron Microscopic ◽  
Normal Human Skin ◽  
Type Iv ◽  
Type Vii Collagen ◽  
Keratin Filaments ◽  
Normal Human ◽  
Phosphate Buffered Saline

1nm colloidal gold with silver enhancement has been used in conjunction with a low-temperature post-embedding (post-E) technique for the demonstration of skin antigens at both the light microscopic (LM) and electron microscopic (EM) levels.Keratin filaments and basement membrane zone (BMZ) associated antigens in normal human skin (NHS) were immunolabelled using antibodies against keratin 14, 10, and 1, the carboxy-terminus and collagenous portion of type VII collagen, type IV collagen and bullous pemphigoid antigen (BP-Ag).Fresh samples of NHS were cryoprotected in 15% glycerol, cryofixed in propane at -190°C, subjected to freeze substitution in methanol at -80°C and embedded in Lowicryl K11M at -60°C. Polymerisation of the resin was initiated under UVR at - 60°C for 48 hours and continued at room temperature for a further 48 hours. Semith in sections were air dried onto slides coated with 3-aminopropyltriethoxysilane. The following immunolabelling protocol was adopted: Primary antibody was applied for 2 hours at 37°C or overnight at 4°C. Following washing in Dulbecco’s phosphate buffered saline (PBSA) a biotinylated secondary antibody was applied for 2 hours at 37°C. The sections were further washed in PBSA and 1nm gold avidin was applied. Sections were finally washed in PBSA and silver enhanced.

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