Expression Of Matrix Metalloproteinase-10 Research Articles

Dampening of proteomics activity associated with the COVID-19 patients afflicted with asthma based on gene expression pattern

Introduction. It is established that the severity of SARS-CoV-2 infections varies between individuals without underlying health conditions and those with chronic illnesses like asthma.
 Aim: to assess the gene expression of COVID-19 patients with and without asthma.
 Materials and Methods. 20 patient profiles out of a total of 288 were selected from Gene Expression Omnibus (GSE178399). All patients have positive PCR tests and were divided into 4 groups. GEO2R was used to estimate the comparison between groups. STRING tool was used to measure the correlation between genes. The phylogenetic tree was extracted using iTOL. The heat map was extracted using iDEP.96.
 Results. MMP10 (Matrix metalloproteinase-10), TNFRSF11B (Tumor necrosis factor receptor superfamily member 11B), CCL23 (C-C motif chemokine ligand 23), CD274 (Programmed cell death 1) CX3CL1 (C-X3-C motif chemokine), and IL17C (Interleukin-17C) had down-regulation for all patients. Transcriptome data conducted no correlation between the expression of MMP10 and asthma, although there is a significant correlation between the expression of MMP1 and sensitivity. The expression of IL17A, which is strongly related to allergic asthma, is decreased in non-asthmatic individuals but elevated in asthmatic patients, notably in survivors. Patients who were not asthmatic had significantly higher CXCL9 levels.
 Conclusions. The study revealed a disparity in the relationship between imbalanced gene expressions in the groups examined. The gene expression of asthma patients who survived and died was not significantly different.

MMP-10 Deficiency Effects Differentiation and Death of Chondrocytes Associated with Endochondral Osteogenesis in an Endemic Osteoarthritis.

ObjectiveThe objective of this study was to determine the matrix metalloproteinase-10 (MMP-10) expression pattern and to assess how it contributes to endochondral osteogenesis in Kashin-Beck disease (KBD).DesignThe cartilages of KBD patients, Sprague-Dawley rats fed with selenium (Se)-deficient diet and/or T-2 toxin, and ATDC5 cells were used in this study. ATDC5 cells were induced into hypertrophic chondrocytes using a 1% insulin-transferrin-selenium (ITS) culture medium for 21 days. The expressions of MMP-10 in the cartilages were visualized by immunohistochemistry. The messenger RNA (mRNA) and protein expression levels were determined by real-time polymerase chain reaction (RT-PCR) and Western blotting. MMP-10 short hairpin RNA (shRNA) was transfected into hypertrophic chondrocytes to knock down the gene expression of MMP-10. Meanwhile, the cell death of MMP-10-knockdown chondrocyte was detected using flow cytometry.ResultsThe expression of MMP-10 was decreased in the growth plates of children with KBD. A decreased expression of MMP-10 also was observed in the growth plates of rats fed with an Se-deficient diet and/or T-2 toxin exposure. The mRNA and protein expression levels of MMP-10 increased during the chondrogenic differentiation of ATDC5 cells. MMP-10 knockdown in hypertrophic chondrocytes significantly decreased the gene and protein expression of collagen type II (Col II), Col X, Runx2, and MMP-13. Besides, the percentage of cell apoptosis was significantly increased after MMP-10 knockdown in hypertrophic chondrocytes.ConclusionMMP-10 deficiency disrupts chondrocyte terminal differentiation and induces the chondrocyte’s death, which impairs endochondral osteogenesis in the pathogenesis of KBD.

Matrix Metalloproteinase-10 in Kidney Injury Repair and Disease.

Matrix metalloproteinase-10 (MMP-10) is a zinc-dependent endopeptidase with the ability to degrade a broad spectrum of extracellular matrices and other protein substrates. The expression of MMP-10 is induced in acute kidney injury (AKI) and chronic kidney disease (CKD), as well as in renal cell carcinoma (RCC). During the different stages of kidney injury, MMP-10 may exert distinct functions by cleaving various bioactive substrates including heparin-binding epidermal growth factor (HB-EGF), zonula occludens-1 (ZO-1), and pro-MMP-1, -7, -8, -9, -10, -13. Functionally, MMP-10 is reno-protective in AKI by promoting HB-EGF-mediated tubular repair and regeneration, whereas it aggravates podocyte dysfunction and proteinuria by disrupting glomerular filtration integrity via degrading ZO-1. MMP-10 is also involved in cancerous invasion and emerges as a promising therapeutic target in patients with RCC. As a secreted protein, MMP-10 could be detected in the circulation and presents an inverse correlation with renal function. Due to the structural similarities between MMP-10 and the other MMPs, development of specific inhibitors targeting MMP-10 is challenging. In this review, we summarize our current understanding of the role of MMP-10 in kidney diseases and discuss the potential mechanisms of its actions.

Identification of matrix metalloproteinase-10 as a key mediator of podocyte injury and proteinuria

Podocyte injury or dysfunction plays an essential role in causing proteinuria and glomerulosclerosis in chronic kidney diseases. To search for new players involved in podocyte injury, we performed gene expression profiling in the glomeruli by RNA sequencing. This unbiased approach led us to discover matrix metalloproteinase-10 (MMP-10), a secreted zinc-dependent endopeptidase, as one of the most upregulated genes after glomerular injury. In animal models and patients with proteinuric chronic kidney diseases, MMP-10 was upregulated specifically in the podocytes of injured glomeruli. Patients with chronic kidney diseases also had elevated circulating levels of MMP-10, which correlated with the severity of kidney insufficiency. In transgenic mice with podocyte-specific expression of MMP-10, proteinuria was aggravated after injury induced by Adriamycin. This was accompanied by more severe podocytopathy and glomerulosclerotic lesions. In contrast, knockdown of MMP-10 invivo protected mice from proteinuria, restored podocyte integrity and reduced kidney fibrosis. Interestingly, MMP-10 reduced podocyte tight junctional protein zonula occludens-1 (ZO-1) but did not affect its mRNA level. Incubation of purified ZO-1 with MMP-10 directly resulted in its proteolytic degradation invitro, suggesting ZO-1 as a novel substrate of MMP-10. Thus, our findings illustrate that induction of MMP-10 could lead to podocyte injury by degrading ZO-1, thereby promoting proteinuria and glomerulosclerosis in chronic kidney diseases.

β-Carotene Inhibits Expression of Matrix Metalloproteinase-10 and Invasion in Helicobacter pylori-Infected Gastric Epithelial Cells.

Matrix metalloproteinases (MMPs), key molecules of cancer invasion and metastasis, degrade the extracellular matrix and cell–cell adhesion molecules. MMP-10 plays a crucial role in Helicobacter pylori-induced cell-invasion. The mitogen-activated protein kinase (MAPK) signaling pathway, which activates activator protein-1 (AP-1), is known to mediate MMP expression. Infection with H. pylori, a Gram-negative bacterium, is associated with gastric cancer development. A toxic factor induced by H. pylori infection is reactive oxygen species (ROS), which activate MAPK signaling in gastric epithelial cells. Peroxisome proliferator-activated receptor γ (PPAR-γ) mediates the expression of antioxidant enzymes including catalase. β-Carotene, a red-orange pigment, exerts antioxidant and anti-inflammatory properties. We aimed to investigate whether β-carotene inhibits H. pylori-induced MMP expression and cell invasion in gastric epithelial AGS (gastric adenocarcinoma) cells. We found that H. pylori induced MMP-10 expression and increased cell invasion via the activation of MAPKs and AP-1 in gastric epithelial cells. Specific inhibitors of MAPKs suppressed H. pylori-induced MMP-10 expression, suggesting that H. pylori induces MMP-10 expression through MAPKs. β-Carotene inhibited the H. pylori-induced activation of MAPKs and AP-1, expression of MMP-10, and cell invasion. Additionally, it promoted the expression of PPAR-γ and catalase, which reduced ROS levels in H. pylori-infected cells. In conclusion, β-carotene exerts an inhibitory effect on MAPK-mediated MMP-10 expression and cell invasion by increasing PPAR-γ-mediated catalase expression and reducing ROS levels in H. pylori-infected gastric epithelial cells.

RACK1 to modulate expression of MMP10 via Src/NF-κB pathway in gastric cancer.

e15529 Background: Receptor of activated C kinase 1 (RACK1) is regarded as a scaffolding protein in multiple intracellular signal transduction pathways. Our previous works had demonstrated that RACK1 might involve in progression of gastric cancer, and could be a criterion to predict the good prognosis for the patients after surgical resection. The aim of this study is to explore the regulatory role of RACK1 in matrix metalloproteinase 10 (MMP10) autocrine, and which may be involved in invasion of gastric cancer. Methods: RACK1 knockdown gastric cell lines were established by shRNA. Secretion of cytokines secretion, as well as MMP10 was measured by antibody arrays and enzyme-linked immunosorbent assay. Cell migration and invasion was compared between normal and RACK1 knockdown cells. Pharmacological inhibitors were employed in searching specific signaling pathway. The correlation of RACK1 and MMP10 expression in gastric cancer samples was analyzed by Spearman’s ρ test. Results: Expression of MMP10 was substantially enhanced after knockdown of RACK1 in vitro, which contributed to enhanced migration and invasiveness of gastric cancer cells in autocrine manner. Specific inhibitors of NF-κB and c-Src, as well as overexpression of dominant-negative c-Src mutant, could suppress the expression of MMP10. Finally, an inverse correlation of RACK1 and IL-8 expression was confirmed in gastric cancer samples. Conclusions: Down-regulation of RACK1 resulted in the up-regulation of MMP10 in gastric cancer, which might enhance invasiveness via Src/NF-κB pathway partially.

Differential immunohistochemical expression of matrix metalloproteinase-10 (MMP-10) in non-melanoma skin cancers of the head and neck

Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC) are two common skin malignancies with different potentials for invasion and metastasis. The mechanism responsible for various growth patterns observed in SCC and BCC is still not fully understood. The aim of this study was to investigate the expression of matrix metalloproteinase-10 in non-melanoma skin cancers, including BCC and SCC of the head and neck.The study group consisted of 60 specimens, including 30 BCC and 30 cutaneous SCC of the head and neck. Sections of tumor biopsy samples were immunohistochemically examined for the expression of MMP-10. Data were analyzed by SPSS (V.21) using Mann-Whitney and Kruskal Wallis tests.We found higher immunohistochemical expression of MMP-10 in tumor epithelium and stroma of SCC as compared with BCC. However, this difference was significant only in tumor epithelium (P=0.000). Moreover, the level of MMP-10 expression in tumor epithelium of grades III and II of SCC was significantly greater compared to grade I tumors (P<0.05).Our results suggest that the level of the MMP-10 expression in tumor epithelium of cutaneous SCC and BCC may contribute to the different invasive patterns observed in these tumors. Also, the expression of MMP-10 is associated with tumor differentiation in cutaneous HNSCC.

Characterization of a P-Rex1 gene signature in breast cancer cells.

The Rac nucleotide Exchange Factor (Rac-GEF) P-Rex1 is highly expressed in breast cancer, specifically in the luminal subtype, and is an essential mediator of actin cytoskeleton reorganization and cell migratory responses induced by stimulation of ErbB and other tyrosine-kinase receptors. Heregulin (HRG), a growth factor highly expressed in mammary tumors, causes the activation of P-Rex1 and Rac1 in breast cancer cells via ErbB3, leading to a motile response. Since there is limited information about P-Rex1 downstream effectors, we carried out a microarray analysis to identify genes regulated by this Rac-GEF after stimulation of ErbB3 with HRG. In T-47D breast cancer cells, HRG treatment caused major changes in gene expression, including genes associated with motility, adhesion, invasiveness and metastasis. Silencing P-Rex1 expression from T-47D cells using RNAi altered the induction and repression of a subset of HRG-regulated genes, among them genes associated with extracellular matrix organization, migration, and chemotaxis. HRG induction of MMP10 (matrix metalloproteinase 10) was found to be highly sensitive both to P-Rex1 depletion and inhibition of Rac1 function by the GTPase Activating Protein (GAP) β2-chimaerin, suggesting the dependence of the P-Rex1/Rac1 pathway for the induction of genes critical for breast cancer invasiveness. Notably, there is a significant association in the expression of P-Rex1 and MMP10 in human luminal breast cancer, and their co-expression is indicative of poor prognosis.

Expression of Matrix Metalloproteinase-10 at Invasive Front of Squamous Cell Carcinoma and Verrucous Carcinoma in the Oral Cavity.

Matrix metalloproteinases (MMPs) are a family of zinc metalloproteinases capable of degrading components of connective tissues. MMP-10 is frequently expressed in human cancers. The aim of this study was to immunohistochemically evaluate its expression in oral squamous cell carcinoma (OSCC) and verrucous carcinoma (OVC). A retrospective analysis of 73 samples (31 OSCC, 22 OVC and 20 non-neoplastic epithelium) was performed. All samples were immunohistochemically stained with monoclonal MMP-10 antibody and expression levels and staining intensity were evaluated with respect to microscopic features. Data were analyzed by SPSS (V.21), Mann-Whitney and Kruskal Wallis tests. MMP-10 was detected in all OSCC and OVC cases. The expression of MMP-10 in OSCC was intensive (score 3) and in OVC was low and moderate (score 1 and score 2) more frequently. Non- neoplastic epithelium did not show MMP-10 expression. Differences between groups was statistically significant (p<0.05). However, the expression of MMP- 10 was not obviously different between various grades of OSCC. According to our study, MMP-10 protein can be important possible factor in the transformation of normal oral epithelium to OVC and OSCC, also the level of MMP-10 expression at invasion front of the lesions can be helpful in the differentiation of OVC and OSCC.

Expression of matrix metalloproteinase-10 in non-metastatic prostate cancer: Correlation with an imbalance in cell proliferation and apoptosis

Matrix metalloproteinases (MMPs) are associated with cell invasion under various physiological and pathological conditions. Among MMPs, MMP-10 is reported to correlate with a high pT stage and progression in a variety of cancer types. However, the clinical and pathological significance of MMP-10 in human prostate cancer tissues remains unclear. This study aimed to clarify the role of MMP-10 in non-metastatic prostate cancer. Sixty-three specimens were obtained by radical prostatectomy. MMP-10 expression, Ki-67, CD34 and apoptotic cells were examined using an immunohistochemical technique and the terminal deoxynucleotidyl transferase-mediated nick end-labeling method. The proliferation index (PI), apoptotic index (AI), microvessel density (MVD) and cell renewal index (CRI=PI/AI) were calculated. The relationship between MMP-10 expression and clinicopathological features, as well as PI, AI, MVD and CRI were investigated. MMP-10 was mainly detected in cancer cell cytoplasm, and the proportion of MMP-10-expressing cancer cells (median 13.8%) was significantly higher (P<0.001) than non-tumoral gland cells (2.4%). Similarly, the proportion of MMP-10-expressing cancer cells was significantly higher (P=0.007) in stage pT3 (median 22.3%) than in pT2 (11.3%) tumors and was correlated with blood vessel invasion (P=0.025). In addition, its expression level correlated significantly with CRI (r=0.34, P=0.001), but not with PI, AI or MVD. Multivariate analysis identified MMP-10 expression to be closely associated with pT stage (OR 3.76, 95% CI 1.14-12.34, P=0.029). Our results suggest that the overexpression of MMP-10 produces an imbalance in cancer cell proliferation and apoptosis, thereby contributing to cancer cell progression of non-metastatic prostate cancer.

Abstract 1351: Lack of matrix metalloproteinase-10 exacerbates inflammation-associated colon tumor development

Abstract Ulcerative colitis is the most common inflammatory bowel disease, and is associated with increased risk of colon cancer. Understanding the mechanisms by which carcinogenesis occurs in the setting of colitis could lead to both prevention strategies and improved therapies. Matrix metalloproteinase-10 (MMP10), a member of the matrix metalloproteinase family of proteolytic enzymes, is expressed at healing edges of colonic ulcers. Although MMPs are usually considered as destructive players in inflammatory disease, we considered the possibility that MMP10 had a beneficial role in ulcerative colitis. We used dextran sulfate sodium (DSS) treatment in MMP10-null and corresponding control wild-type mice to investigate the consequences of MMP10 deletion on colitis development and recovery. Groups of mice were exposed to DSS for 7-day periods and sacrificed at different timepoints following the cessation of the DSS. Strikingly, MMP10-null mice were more severely affected by the treatment as determined by gross observations such as weight loss and colon length. Histological analysis at the various timepoints indicated that wild-type mice showed almost complete recovery from DSS within 14 days after DSS treatment. In contrast, MMP10-null mice still showed clear signs of damage with persistent inflammatory foci and non-healing ulcers. In situ hybridization indicated MMP10 expression predominantly in inflammatory cells, although some fibroblasts were also positive. Colonic epithelium was negative for MMP10. Bone marrow transplant experiments indicated that wild-type bone marrow partially rescued the MMP10-null phenotype. Measurement of cytokines by ELISA in colonic lavage fluid from MMP10-null and wild-type mice showed that IL-1α was significantly increased in the absence of MMP10. Levels of other cytokines such as TNFα, IL6, IL17 and G-CSF were not different. Multiple exposures to DSS results in conversion of an acute colitis to a chronic inflammatory disease. With only 2 DSS exposures, MMP10-null mice manifested a chronic condition which failed to resolve even after 3 months. Similarly-treated wild-type mice, however, appeared normal at this timepoint. Examination of the colonic tissue from the DSS double exposure showed a significant increase in the number of dysplastic foci present in the MMP10-null mice. Thus, expression of MMP10 appears necessary for resolution of colitis, and in its absence, the development of chronic colitis results in tumor development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1351.

Increased expression of matrix metalloproteinase-10, nerve growth factor and substance P in the painful degenerate intervertebral disc

IntroductionMatrix metalloproteinases (MMPs) are known to be involved in the degradation of the nucleus pulposus (NP) during intervertebral disc (IVD) degeneration. This study investigated MMP-10 (stromelysin-2) expression in the NP during IVD degeneration and correlated its expression with pro-inflammatory cytokines and molecules involved in innervation and nociception during degeneration which results in low back pain (LBP).MethodsHuman NP tissue was obtained at postmortem (PM) from patients without a history of back pain and graded as histologically normal or degenerate. Symptomatic degenerate NP samples were also obtained at surgery for LBP. Expression of MMP-10 mRNA and protein was analysed using real-time polymerase chain reaction and immunohistochemistry. Gene expression for pro-inflammatory cytokines interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-α), nerve growth factor (NGF) and the pain-associated neuropeptide substance P were also analysed. Correlations between MMP-10 and IL-1, TNF-α and NGF were assessed along with NGF with substance P.ResultsMMP-10 mRNA was significantly increased in surgical degenerate NP when compared to PM normal and PM degenerate samples. MMP-10 protein was also significantly higher in degenerate surgical NP samples compared to PM normal. IL-1 and MMP-10 mRNA demonstrated a significant correlation in surgical degenerate samples, while TNF-α was not correlated with MMP-10 mRNA. NGF was significantly correlated with both MMP-10 and substance P mRNA in surgical degenerate NP samples.ConclusionsMMP-10 expression is increased in the symptomatic degenerate IVD, where it may contribute to matrix degradation and initiation of nociception. Importantly, this study suggests differences in the pathways involved in matrix degradation between painful and pain-free IVD degeneration.

Celecoxib Inhibits Serum Amyloid A-Induced Matrix Metalloproteinase-10 Expression in Human Endothelial Cells

Background: Although serum amyloid A (SAA) is an established biomarker of coronary artery disease (CAD), its direct role in matrix degradation is obscure. This study investigated the effect of SAA on the expression of matrix metalloproteinase-10 (MMP-10) in endothelial cells. The effect of celecoxib on SAA-dependent MMP-10 expression and its possible mediator were also investigated. Methods and Results: From our time course microarray screening, SAA (20 μg/ml) was found to increase MMP-10 mRNA expression over time (4–48 h) in human endothelial cells. Quantitative real-time PCR confirmed this transcriptional induction. Correspondingly, secreted MMP-10 protein was also markedly induced by SAA treatment for 24 h in a dose-dependent manner. We further examined cyclooxygenase-2 (COX-2) and its major product, prostaglandin E₂ (PGE₂), as possible mediators of MMP-10 induction. Direct PGE₂ treatment could result in MMP-10 induction. Celecoxib, a selective COX-2 inhibitor, suppressed MMP-10 secretion induced by SAA. Conclusions: SAA induced MMP-10 expression and celecoxib prevented its induction. MMP-10 induction was at least partly mediated by PGE₂.

Expression of Matrix Metalloproteinase-10 in Renal Cell Carcinoma and Its Prognostic Role

ObjectivesMatrix metalloproteinase (MMP)-10 is associated with malignant aggressiveness in various cancers, but its importance has not been investigated in conventional renal cell carcinoma (CRCC). The purpose of this study was to determine the clinical significance and malignant potential of MMP-10 in human CRCC tissues. Patients and methodsSpecimens were obtained from 103 CRCC patients who underwent radical surgery and were examined by immunohistochemistry for MMP-10 expression. The proportions of Ki-67–stained cells (proliferation index: PI) and densities of CD34-positive vessels (microvessel density: MVD) were measured by a computer-aided image analysis system. The relationships between MMP-10 expression and clinicopathologic features and various parameters including tumour size, PI, MVD, and survival were investigated by univariate and multivariate analyses. ResultsMMP-10 expression was mainly detected in cancer cell cytoplasm, and 45 (43.7%) CRCCs were considered MMP-10–positive. MMP-10 expression correlated with grade (p=0.006) and pT stage (p<0.001), and it was a significant and independent factor for high pT stage in multivariate analysis model. MMP-10 expression was associated with MVD (p=0.022) but not tumour size or PI. MMP-10 expression in CRCC was a significant predictor of poor outcome by log-rank test (p=0.013) but not by multivariate analysis. ConclusionsMMP-10 seems to play an important role in renal cancer cell invasion and is a potentially useful therapeutic target to prevent CRCC tumour progression.

Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer

Gastric cancer (GC) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue will be useful molecular markers for diagnosis and may also be good therapeutic targets. However, little is known about cancer-specific genes, at least in GC. In this study, we searched for GC-specific genes by serial analysis of gene expression (SAGE) data analysis and quantitative reverse transcription (RT)-PCR. Comparing GC SAGE libraries with those of various normal tissues in the SAGEmap database, we identified 54 candidate GC-specific genes. Quantitative RT-PCR analysis of these candidates revealed that APin protein (APIN), taxol resistance-associated gene 3 (TRAG3), cytochrome P450, family 2, subfamily W, polypeptide 1 (CYP2W1), melanoma inhibitory activity (MIA), matrix metalloproteinase-10 (MMP-10), dickkopf homolog 4 (DKK4), GW112, regenerating islet-derived family, member 4 (REGIV), and HORMA domain-containing 1 (HORMAD1) were expressed much more highly in GC than in 14 kinds of normal tissues. Immunohistochemical staining for MIA, MMP-10, and DKK4 was found in 47 (31.1%), 68 (45.0%), and two (1.3%) of 151 GCs, respectively, and staining for both MIA and MMP-10 was correlated with poor prognosis in advanced GC (P=0.0001 and 0.0141, respectively). Moreover, enzyme-linked immunosorbent assay showed high levels of MMP-10 (65/69, 94.2%) in serum samples from patients with GC. Levels of MIA were raised in a small proportion of serum samples from patients with GC (4/69, 5.8%). In Boyden chamber invasion assays, MIA-transfected GC cells were up to three times more invasive than cells transfected with empty vector. Taken together, these results suggest that MMP-10 is a good marker for the detection of GC and that MIA and MMP-10 are prognostic factors for GC. As expression of MIA and MMP-10 is narrowly restricted in cancer, these two molecules may be good therapeutic targets for GC.

Expression of matrix metalloproteinase-10 in human bladder transitional cell carcinoma

Objectives To analyze matrix metalloproteinase-10 (MMP-10) expression in transitional cell carcinoma (TCC) of the bladder, evaluate the correlations between MMP-10 protein expression and clinicopathologic parameters, and address the viability of MMP-10 as a therapeutic target for TCC. MMP-mediated degradation of the extracellular matrix is an important factor in the pathogenesis of tumorigenesis and metastasis. Methods Using immunohistochemistry, the expression of MMP-10 was assessed using both tissue microarrays and whole sections of archival tissue specimens representative of all grades and stages of human bladder TCC (n = 60). MMP-10 expression was also assessed in histologically normal human bladder tissue (n = 10). The immunostaining results for MMP-10 expression were examined for correlations with tumor grade and stage. Results Unlike most MMPs, MMP-10 was localized primarily in the tumor mass as opposed to the tumor stroma and was detectable in all grades and stages of TCC. Significantly greater levels of MMP-10 protein were observed in superficial (pTa, pT1; n = 38) tumors than in normal bladder tissue ( P = 0.01). In contrast to the proposed role of MMPs in tumor invasion, no significant difference was observed between muscle-invasive tumors (pT2 or worse; n = 22) and histologically normal bladder tissue ( P = 0.50). MMP-10 expression showed no significant correlation with tumor grade. Conclusions The data from our study showed that, unlike most MMPs, MMP-10 was not associated with tumor aggression or invasion. Our results suggest that MMP-10 protein levels are significantly greater in the earlier stages of TCC development.

Interleukin-6 treatment augments cutaneous wound healing in immunosuppressed mice.

It has been postulated that the inflammatory response that occurs after cutaneous wounding is a prerequisite for healing and that inflammatory cytokines, such as interleukin-6 (IL-6) are involved in this process. We showed previously that IL-6-deficient mice display delayed wound healing, which could be reversed by administration of a murine IL-6 expression plasmid or recombinant murine IL-6 (rMuIL-6). In the present study, we observed that delayed cutaneous wound healing, which occurs as a result of glucocorticoid-induced immunosuppression, can also be reversed by rMuIL-6, as evidenced by epithelialization, granulation tissue formation, and wound closure. In vehicle control mice, rMuIL-6 did not augment healing but rather delayed the process. Immunochemical studies indicated that the expression of matrix metalloproteinase-10 (MMP-10) was increased in dexamethasone-treated mice and that rMuIL-6 treatment reduced its expression, indicating that IL-6 may influence dermal matrix formation and, specifically, collagen synthesis. These results demonstrate that IL-6 can restore abnormal wound repair that occurs in immunodeficiency and suggest its use as a potential therapy.