Matrix Metalloproteinase Inhibitor RECK Expression in Canine Tumors (original) (raw)
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Molecular Cloning of Canine Membrane-Anchored Inhibitor of Matrix Metalloproteinase, RECK
Journal of Veterinary Medical Science, 2005
The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene is one of the endogenous matrix metalloproteinase (MMP) inhibitors. It was reported that decreased RECK expression closely correlated with tumor malignancy. We determined the cDNA sequence of the canine RECK gene. The cDNA sequence and deduced amino acid of canine RECK were 2,913 bases and 971 residues, respectively. The predicted amino acid sequence of the protein showed 95.5% and 91.9% homology with human and mouse RECK, respectively. RECK mRNA expression was analyzed in various canine tissues and tumor cell lines by quantitative RT-PCR. The highest RECK expression was detected in lung and testis. In comparison with the tissues, a remarkably low expression level was detected in tumor cell lines. In addition, the RECK gene was transfected in the canine transitional cell carcinoma, and its influence on cell proliferation, migration, and invasion was analyzed. The transfected RECK gene suppressed only canine tumor invasion. These results showed that RECK might play an important role in tumor malignancy in dogs as well as in other mammalians.
Journal of Gastroenterology, 2011
Background Reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) has been implicated in the attenuation of tumor metastasis by negatively regulating metalloproteinase (MMP) levels. RECK gene expression is downregulated in many solid tumors, with this downregulation being associated with poor prognosis. This study evaluated the role of RECK in cholangiocarcinoma (CCA). Methods The expression of RECK, MMP-2, and MMP-9 in paraffin sections of hamster and human CCA specimens was analyzed by immunohistochemistry. Functional analysis of RECK was performed in RECK small interfering (si) RNA knockdown CCA cell lines. The effect of aspirin on RECK status and function was evaluated using Western blotting, gelatin zymography, invasion and proliferation assays, and PhosphoELISArray analysis of Ras downstream mediators. Results Hamster tissues showed high RECK expression in hyperplastic biliary duct epithelia, low RECK expression in precancerous lesions, and no RECK expression in CCA. In human specimens, RECK was highly expressed in normal biliary cells, whereas intrahepatic CCA showed low levels of expression. Downregulation of RECK was correlated with tumor metastasis (P < 0.01) and shorter patient survival (P < 0.02). RECK expression levels were inversely correlated with MMP-2 and MMP-9 expression (P < 0.05). SiRNA RECK-depleted M139 CCA cells exhibited increased MMP-2/-9 gelatinase activities and invasiveness. Aspirin (500 μM) demonstrated myriad effects in human CCA cell lines, including growth suppression, reduced phosphorylation of Akt/Erk/c-Jun, elevation of RECK expression, inhibition of MMP-2/MMP-9 activity, and enhanced invasiveness. Conclusions RECK functions as a metastasis suppressor in CCA; upregulation of RECK expression could provide a potential therapy to improve the prognosis of this type of cancer.
Cancer Letters, 2006
mRNA, and latent and active levels MMP-2 and -9 were higher in tumor tissue compared to normal tissue from 63 patients with colorectal cancer, whereas RECK and EMMPRIN levels were lower. Correlations between mRNA, latent, and active MMP were particular high for MMP-2 in tumor tissue (R s Z0.6-0.8, P!0.001). For active MMP-2, but not for MMP-9, a significant negative partial correlation (R p ZK0.440, P!0.001) for RECK was found in tumor tissue, which was confirmed by linear regression analysis. In exploratory survival analyses we found that in patients with localized disease the RECK level in normal or tumor tissue had a significant (PZ0.017) association with overall survival. q
Mehmet Akif Ersoy Üniversitesi Veteriner Fakültesi Dergisi, 2018
Transmissible venereal tumor (TVT) is a sexually transmitted, naturally occurring tumor of the canine family and often occurs in tropical and subtropical countries. The matrix metalloproteinases (MMPs) are endogenous proteases accountable for the degradation of extracellular matrix (ECM) components, such as collagen and other proteins including the basement membrane. MMPs play a vital role in the tumor metastasis and angiogenesis. Both MMP-2 and-7 strongly associated with the invasion and metastasis of different cancer types. This study aims to investigate the MMP-2 and-7 expression in naturally occurring TVT in 20 dogs using immunohistochemical methods. Immunohistochemically, we observed increased MMP-2 and-7 expressions in tumor cells. In addition, a positive correlation was determined between the tumor size and immunoexpressions of the markers indicating that both MMP-2 and-7 participate in the TVT pathogenesis. Köpek transmissible venereal tümörlerinde mmp-2 ve mmp-7 aktivitesinin immunohistokimyasal olarak belirlenmesi ÖZ Transmissible venereal tümör (TVT), çiftleşmeyle bulaşan, kanidae ailesindeki hayvanlarda doğal olarak şekillenen, genellikle tropikal ve subtropikal ülkelerde gözlenen bir tümördür. Matriks metalloproteinazlar (MMP)'ler endojen peptidazlar olup, ekstraselüler matriksin (ECM) kollagen ve bazal membran gibi diğer proteinlerini parçalama özelliğine sahiptirler. MMP'ler tümör metastaz ve angiogenezinde önemli rol oynarlar. MMP-2 ve MMP-7 değişik tip kanserlerde invazyon ve metastaz ile ilişkili bulunmuşlardır. Bu çalışmanın amacı, MMP-2 ve MMP-7'nin 20 adet köpekte doğal olarak şekillenmiş TVT olgusunda immunhistoimyasal olarak ekspresyonlarının incelenmesidir. İmmunohistokimyasal olarak TVT'yi oluşturan tümör hücrelerde MMP-2 ve MMP-7 aktivitesinde artış şekillendiği gözlendi. Ayrıca tümör büyüklüğü ile immunoekspresyonlar arasında pozitif korelasyon saptandı, bu sonuç, MMP-2 ve MMP-7'in TVT patojenezinde önemli bir rol oynadığını gösterdi.
Matrix metalloproteinase inhibitor reversion‐inducing cysteine‐rich protein with Kazal motifs
Cancer, 2003
BACKGROUNDThe recently described reversion‐inducing cysteine‐rich protein with Kazal motifs (RECK) inhibits membrane Type 1 matrix metalloproteinase (MMP‐14), MMP‐2, and MMP‐9 secretion and enzymatic activity. Its expression is essential for normal vasculogenesis. Down‐regulation of RECK has been implicated in tumor angiogenesis and progression.METHODSThe authors assessed the prognostic value of RECK expression in tumor tissue specimens from 278 breast carcinoma patients with a median follow‐up time of 75 months (range, 2–169 months). RECK mRNA levels were measured by real‐time quantitative reverse transcriptase–polymerase chain reaction.RESULTSExpression levels of RECK were lower in tumor tissue specimens than in adjacent normal breast tissue specimens from 10 patients (P = 0.028). No relevant associations of RECK with established clinicopathologic factors or treatment regimens were found. RECK expression predicted a longer recurrence‐free survival time (RFS; P = 0.037) at the opti...
Identification of matrix metalloproteinases in canine neoplastic tissue
American Journal of Veterinary Research, 2000
Presence of matrix metalloproteinases has been associated with tumor invasion and metastasis in human neoplasia. The presence of matrix metalloproteinase 2 and matrix metalloproteinase 9 was determined in canine mast cell tumor tissue and normal stromal tissue from 24 dogs with spontaneously occurring cutaneous mast cell tumors. Seventeen of the mast cell tumors were of histologic grade 2, and 7 were of histologic grade 3. Gelatin zymography and computer assisted densitometry image analysis were used to quantify matrix metalloproteinase concentration. Bands from canine tissues migrated in the same location as human proenzyme and active enzyme matrix metalloproteinase 2 and matrix metalloproteinase 9 standards. A semiquantitative value for each patient sample was obtained by comparing the optical assessment density of each unknown band to the optical density of the human standard. The presence of matrix metalloproteinase 2 and matrix metalloproteinase 9 in histologic grade 2 mast cell tumors and histologic grade 3 mast cell tumors was compared, as was presence of matrix metalloproteinases in tumor and stromal tissue. There was dramatically more proenzyme matrix metalloproteinase 9 activity in histologic grade 3 mast cell tumors when compared to grade 2 tumors (P ϭ .03). There was also dramatically more active enzyme matrix metalloproteinase 2 and active enzyme matrix metalloproteinase 9 activity in tumor tissue compared to stromal tissue (P ϭ .02, P Ͻ .0001). This study demonstrates that the proenzyme and active enzyme forms of matrix metalloproteinase 2 and matrix metalloproteinase 9 are present in canine mast cell tumors. This appears to be related to the degree of histologic malignancy, although histologic grade 1 tumors were not evaluated.
Matrix metalloproteinases and their inhibitors in canine mammary tumors
BMC Veterinary Research, 2011
Background Malignant canine mammary tumors represent 50% of all neoplasms in female dogs. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be involved in tumor progression, and they are also associated with the reactive stroma, which provides structural and vascular support for tumor growth. Results MMP-2, MMP-9 and MT1-MMP were expressed at both the mRNA and protein levels
Frontiers in Molecular Biosciences
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that regulate the turnover of extracellular matrix (ECM) components. Gross and La Piere discovered MMPs in 1962 during an experiment on tissue samples from a tadpole’s tail. Several subtypes of MMPs have been identified, depending on their substrate specificity and localization. MMPs are involved as essential molecules in multiple and diverse physiological processes, such as reproduction, embryonic development, bone remodeling, tissue repair, and regulation of inflammatory processes. Its activity is controlled at various levels such as at transcription level, pro-peptide activation level and by the activity of a family of tissue inhibitors of metalloproteinase, endogenous inhibitors of MMPs. Cancer metastasis, which is the spread of a tumor to a distant site, is a complex process that is responsible for the majority of cancer-related death It is considered to be an indicator of cancer metastasis. During metastasis, t...
American Journal of Veterinary Research, 2011
Objective—To evaluate expression of matrix metalloproteinase (MMP)-2 and -9 and membrane-type 1 MMP (MT1-MMP) in melanocytomas and malignant melanomas of dogs, analyze in vitro production of MMPs by canine melanoma cell lines and primary dermal fibroblasts, and investigate mutual communication between tumor cells and fibroblasts and the influence of collagen on MMP regulation. Sample—35 biopsy specimens from melanocytic tumors and primary dermal fibroblasts of dogs and 3 canine melanoma cell lines (CML-1, CML-10c2, and CML-6M). Procedures—MMP-2, MMP-9, and MT1-MMP were detected in tumor samples by use of immunohistochemical analysis. In vitro production was analyzed via reverse transcriptase-PCR assay, immunocytochemical analysis, zymography, and immunoblotting. Results—MMP-9 was overexpressed in malignant melanomas, compared with expression in melanocytomas, whereas no significant differences in MMP-2 and MT1-MMP immunostaining were detected. Stromal cells also often had positive s...