Matrix Metalloproteinase Family Research Articles

A robust classification-dependent multi-molecular modelling study on some biphenyl sulphonamide based MMP-8 inhibitors

ABSTRACT Matrix metalloproteinases (MMPs) are a group of zinc and calcium-dependent endopeptidases, which contribute to different physiological and biological activities via extracellular matrix (ECM) degradation. Matrix metalloproteinase-8 (MMP-8) belongs to type-II collagenases of the MMP family that has contribution in several physiological disorders such as cardiovascular diseases, joint, renal, digestive and respiratory disorders as well as in cancer. In clinical study, MMP-8 is found to be associated with periodontal disease condition. Therefore, MMP-8 specific inhibitors should be developed to target these disorders. The biphenyl sulphonamide (BPS) moiety is one of the crucial structural characteristics found in several MMP-8 inhibitors. Here, different classification-based molecular modelling methods were used to explore the structural features that lead to the activity variation of a series of MMP-8 inhibitors possessing a BPS moiety. Our current classification-based structural analysis of these BPS-derived MMP-8 inhibitors was able to identify the importance of several structural features such as the tetrahydroisoquinoline and N-Boc pyridyl groups, which have positive influences on MMP-8 inhibition. This study was also reflected the importance of the zinc-binding groups (ZBGs) like the hydroxamate and phosphonate for potent and sub-nanomolar range MMP-8 inhibition, which may benefit the development of highly potent MMP-8 inhibitors.

Dynamic Expression of Membrane Type 1-Matrix Metalloproteinase (Mt1-mmp/Mmp14) in the Mouse Embryo.

MT1-MMP/MMP14 belongs to a subgroup of the matrix metalloproteinases family that presents a transmembrane domain, with a cytosolic tail and the catalytic site exposed to the extracellular space. Deficient mice for this enzyme result in early postnatal death and display severe defects in skeletal, muscle and lung development. By using a transgenic line expressing the LacZ reporter under the control of the endogenous Mt1-mmp promoter, we reported a dynamic spatiotemporal expression pattern for Mt1-mmp from early embryonic to perinatal stages during cardiovascular development and brain formation. Thus, Mt1-mmp shows expression in the endocardium of the heart and the truncus arteriosus by E8.5, and is also strongly detected during vascular system development as well as in endothelial cells. In the brain, LacZ reporter expression was detected in the olfactory bulb, the rostral cerebral cortex and the caudal mesencephalic tectum. LacZ-positive cells were observed in neural progenitors of the spinal cord, neural crest cells and the intersomitic region. In the limb, Mt1-mmp expression was restricted to blood vessels, cartilage primordium and muscles. Detection of the enzyme was confirmed by Western blot and immunohistochemical analysis. We suggest novel functions for this metalloproteinase in angiogenesis, endocardial formation and vascularization during organogenesis. Moreover, Mt1-mmp expression revealed that the enzyme may contribute to heart, muscle and brain throughout development.

Huangqi Shengmai Yin Ameliorates Myocardial Fibrosis by Activating Sirtuin3 and Inhibiting TGF-β/Smad Pathway.

Myocardial fibrosis (MF) is an important pathological process in which a variety of cardiovascular diseases transform into heart failure. The main manifestation of MF is the excessive deposition of collagen in the myocardium. Here, we explored whether Huangqi Shengmai Yin (HSY) can inhibit isoprenaline (ISO)-induced myocardial collagen deposition in rats, thereby reducing the cardiac dysfunction caused by MF. The results of echocardiography showed that HSY upregulated fractional shortening and ejection fraction, and reduced the left ventricular systolic dysfunction in the rats with MF. Pathological results showed that HSY protected myocardium, inhibited apoptosis, and effectively reduced collagen deposition. HSY also inhibited the expression of collagen I and III and α-smooth muscle actin (α-SMA) in the heart tissue. HSY increased the expression of Sirtuin 3 (Sirt3) and inhibited the protein levels of the components in the transforming growth factor-β (TGF-β)/Smad pathway. At the same time, it also regulated the expression of related proteins in the matrix metalloproteinases family. In summary, HSY played a therapeutic role in rats with ISO-induced MF by protecting myocardium and inhibiting collagen deposition. Therefore, HSY is a potential therapeutic agent for ameliorating MF.

Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory Synapses.

Long-term synaptic plasticity is shaped by the controlled reorganization of the synaptic proteome. A key component of this process is local proteolysis performed by the family of extracellular matrix metalloproteinases (MMPs). In recent years, considerable progress was achieved in identifying extracellular proteases involved in neuroplasticity phenomena and their protein substrates. Perisynaptic metalloproteinases regulate plastic changes at synapses through the processing of extracellular and membrane proteins. MMP9 was found to play a crucial role in excitatory synapses by controlling the NMDA-dependent LTP component. In addition, MMP3 regulates the L-type calcium channel-dependent form of LTP as well as the plasticity of neuronal excitability. Both MMP9 and MMP3 were implicated in memory and learning. Moreover, altered expression or mutations of different MMPs are associated with learning deficits and psychiatric disorders, including schizophrenia, addiction, or stress response. Contrary to excitatory drive, the investigation into the role of extracellular proteolysis in inhibitory synapses is only just beginning. Herein, we review the principal mechanisms of MMP involvement in the plasticity of excitatory transmission and the recently discovered role of proteolysis in inhibitory synapses. We discuss how different matrix metalloproteinases shape dynamics and turnover of synaptic adhesome and signal transduction pathways in neurons. Finally, we discuss future challenges in exploring synapse- and plasticity-specific functions of different metalloproteinases.

Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening.

Matrix metalloproteinases (MMPs) are the family of proteases that are mainly responsible for degrading extracellular matrix (ECM) components. In the skin, the overexpression of MMPs as a result of ultraviolet radiation triggers an imbalance in the ECM turnover in a process called photoaging, which ultimately results in skin wrinkling and premature skin ageing. Therefore, the inhibition of different enzymes of the MMP family at a topical level could have positive implications for photoaging. Considering that the MMP catalytic region is mostly conserved across different enzymes of the MMP family, in this study we aimed to design a virtual screening (VS) workflow to identify broad-spectrum MMP inhibitors that can be used to delay the development of photoaging. Our in silico approach was validated in vitro with 20 VS hits from the Specs library that were not only structurally different from one another but also from known MMP inhibitors. In this bioactivity assay, 18 of the 20 compounds inhibit at least one of the assayed MMPs at 100 μM (with 5 of them showing around 50% inhibition in all the tested MMPs at this concentration). Finally, this VS was used to identify natural products that have the potential to act as broad-spectrum MMP inhibitors and be used as a treatment for photoaging.

MMP-1 (519 A/G) and TIMP-1 (372 T/C) genes polymorphism in an Egyptian sample of Acne vulgaris patients.

Different Matrix metalloproteinases (MMPs) family members may be implicated in acne vulgaris development. However, there are no published data about the role of MMP-1 and TIMP-1gene polymorphisms in acne vulgaris development. To evaluate the association between MMP-1 (519 A/G) and TIMP-1 (372T/C) gene polymorphisms and the risk of developing acne vulgaris among a sample of Egyptian acne patients. This case-control study included 100 acne vulgaris patients and 120 apparently healthy control subjects. Acne severity was assessed according to Global Acne Grading System (GAGS). MMP-1 (519 A/G) and TIMP-1 (372T/C) gene polymorphisms were investigated using RFLP-PCR technique. The MMP-1 (519 A/G) AG and GG genotypes and G allele increase the risk of acne vulgaris~2-3 folds. In female patients, TIMP-1 (372 C/T) TT genotype and T allele showed significantly higher frequency in cases compared with the control group (p=0.004, 0.001 respectively) with a higher risk to develop acne. On the other hand, in male patients, there was insignificant difference between the frequency of alleles in patients and control subjects. TIMP-1 (372C/T) TT genotype has been shown to be significantly detected in the studied female patients associated with the positive family history of the disease, and it increases the risk of back affection, severe acne grade development, and the liability to postacne scar formation. MMP-1 (519 A/G) and TIMP-1 (372T/C) gene polymorphisms may be related to acne vulgaris development.

A synergy between the catalytic and structural Zn(II) ions and the enzyme and substrate dynamics underlies the structure-function relationships of matrix metalloproteinase collagenolysis.

Matrix metalloproteinases (MMPs) are Zn(II) dependent endopeptidases involved in the degradation of collagen. Unbalanced collagen breakdown results in numerous pathological conditions, including cardiovascular and neurodegenerative diseases and tumor growth and invasion. Matrix metalloproteinase-1 (MMP-1) is a member of the MMPs family. The enzyme contains catalytic and structural Zn(II) ions. Despite many studies on the enzyme, there is little known about the synergy between the two Zn(II) metal ions and the enzyme and substrate dynamics in MMP-1 structure-function relationships. We performed a computational study of the MMP-1•triple-helical peptide (THP) enzyme•substrate complex to provide this missing insight. Our results revealed Zn(II) ions' importance in modulating the long-range correlated motions in the MMP-1•THP complex. Overall, our results reveal the importance of the catalytic Zn(II) and the role of the structural Zn(II) ion in preserving the integrity of the enzyme active site and the overall enzyme-substrate complex synergy with the dynamics of the enzyme and the substrate. Notably, both Zn(II) sites participate in diverse networks of long-range correlated motions that involve the CAT and HPX domains and the THP substrate, thus exercising a complex role in the stability and functionality of the MMP-1•THP complex. Both the Zn(II) ions have a distinct impact on the structural stability and dynamics of the MMP-1•THP complex. The study shifts the paradigm from the "local role" of the Zn(II) ions with knowledge about their essential role in the long-range dynamics and stability of the overall enzyme•substrate (ES) complex.

Matrix Metalloproteinase 3: A Promoting and Destabilizing Factor in the Pathogenesis of Disease and Cell Differentiation.

Cells must alter their expression profiles and morphological characteristics but also reshape the extracellular matrix (ECM) to fulfill their functions throughout their lifespan. Matrix metalloproteinase 3 (MMP-3) is a member of the matrix metalloproteinase (MMP) family, which can degrade multiple ECM components. MMP-3 can activate multiple pro-MMPs and thus initiates the MMP-mediated degradation reactions. In this review, we summarized the function of MMP-3 and discussed its effects on biological activities. From this point of view, we emphasized the positive and negative roles of MMP-3 in the pathogenesis of disease and cell differentiation, highlighting that MMP-3 is especially closely involved in the occurrence and development of osteoarthritis. Then, we discussed some pathways that were shown to regulate MMP-3. By writing this review, we hope to provide new topics of interest for researchers and attract more researchers to investigate MMP-3.

Towards a Better Understanding of the Relationships between Galectin-7, p53 and MMP-9 during Cancer Progression.

It has been almost 25 years since the discovery of galectin-7. This member of the galectin family has attracted interest from many working in the cancer field given its highly restricted expression profile in epithelial cells and the fact that cancers of epithelial origin (carcinoma) are among the most frequent and deadly cancer subtypes. Initially described as a p53-induced gene and associated with apoptosis, galectin-7 is now recognized as having a protumorigenic role in many cancer types. Several studies have indeed shown that galectin-7 is associated with aggressive behavior of cancer cells and induces expression of MMP-9, a member of the matrix metalloproteinases (MMP) family known to confer invasive behavior to cancer cells. It is therefore not surprising that many studies have examined its relationships with p53 and MMP-9. However, the relationships between galectin-7 and p53 and MMP-9 are not always clear. This is largely because p53 is often mutated in cancer cells and such mutations drastically change its functions and, consequently, its association with galectin-7. In this review, we discuss the functional relationships between galectin-7, p53 and MMP-9 and reconcile some apparently contradictory observations. A better understanding of these relationships will help to develop a working hypothesis and model that will provide the basis for further research in the hope of establishing a new paradigm for tackling the role of galectin-7 in cancer.

STRUCTURE AND FUTURE PROSPECTIVE OF MATRIX METALLOPROTEINASES

Matrix metalloproteinases (MMPs) are group of enzymes responsible for the collagen, and protein degradation in extracellular matrix (ECM). Collagen is the main structural component of connective tissue, and its degradation is an important process in the tissue development, remodeling, and repair. MMP family is divided into 6 groups: collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and non-classified MMPs. The MMPs, and MMP inhibitors (MMPI) have multiple biological functions in stages of cancer development. MMPs, and MMPI are extensively examined as potential anticancer medications. The need for selective and metabolically stable MMPs and MMP inhibitors determined the effect of their activity on biological systems. In particular, the relationship of MMPs with the immune system has revealed the potential for the use of MMP inhibitors in therapy. As is known, the degree of invasive growth and metastasis of tumor cells are determined by their ability to cleave all ECM structures of the extracellular matrix - only MMPs can do this. It is important to note that ECM affects the behavior of both cancer cells and stromal, endothelial and immune cells in the environment. The fundamentally important role of ECM is dynamism during tissue homeostasis and the ability to regulate the activation of immune cells.

Abnormal spindle-like microcephaly-associated protein enhances cell invasion through Wnt/β-catenin-dependent regulation of epithelial-mesenchymal transition in non-small cell lung cancer cells.

BackgroundLung cancer is one of the most common cancer worldwide, invasion and metastasis are still the bottleneck in the clinical setting. More diagnostic markers and drug targets need to be clarified. Therefore, we screened abnormal spindle-like microcephaly-associated protein (ASPM) as our candidate gene, which is associated with the poor prognosis. The aim of the present study was to understand the roles of ASPM in cell invasion in non-small cell lung cancer (NSCLC).MethodsGene Expression Omnibus (GEO) datamining was used to identify ASPM. Transwell invasion assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot analysis were performed to discover the molecular functions of ASPM. Overexpression and small interfering mediated knockdown techniques have been used to study the cell invasion hallmarks of cancer.ResultsASPM stood out among all the candidate genes from GEO datamining. ASPM in lung cancer tissues has been associated with poor overall survival rate. The protein levels of ASPM has been validated using lung cancer patients’ tissues, which upregulation of ASPM expression has been found in lung cancer patients. Silencing of ASPM decreased the cell invasion reflected by epithelial-mesenchymal transition (EMT) biomarkers: downregulation of vimentin and upregulation of E-cadherin. Matrix metalloproteinase (MMP) 2/9 protein levels were also affected upon transient knockdown of ASPM. Furthermore, the suppression of ASPM markedly inhibited the Wnt/β-catenin signaling pathway in vitro. The ectopic expression of ASPM had the opposite effect. The inhibition of β-catenin in ASPM-overexpressing lung cancer cells reduced the expression of EMT markers. The inhibitory effects on the Wnt/β-catenin signaling pathway were attenuated in cancer cells when ASPM was silenced. These findings demonstrated that the silencing of ASPM strongly reduced cell invasion in lung cancer.ConclusionsASPM promoted NSCLC invasion through EMT and by affecting the MMP family of proteins. The Wnt/β-catenin signaling pathway played an indispensable role in the ASPM-mediated NSCLC EMT-invasion cascade.

Investigation of the role of matrix metalloproteinases in the genetic etiology of Alzheimer's disease

Matrix metalloproteinases (MMPs) are a multigene family of proteinases regulating the functions of a large number of signaling and scaffolding molecules that are involved in neuro-inflammation, synaptic dysfunction and neuronal death. MMPs have been associated with neurological conditions, such as Alzheimer's disease (AD), through a sudden and massive upregulation of particular members of the MMP family. Evidence for this hypothesis can be found in the clinical observation of increased MMP1 and MMP3 expression levels in plasma of AD patients compared to control individuals and in the pro-amyloidogenic effects that have been described for additional MMP family members like MMP13, MT1-MMP, and MT5-MMP. Consequently, we investigated the role of MMP1, 3, 13, MT1-MMP, and MT5-MMP in the genetic etiology of AD. We performed full exonic resequencing of these 5 MMPs in 1278 AD patients (mean age at onset [AAO]: 74.88 ± 9.10, range: 29–96) and 797 age-matched control individuals (mean age at inclusion [AAI]: 74.92 ± 6.48, range: 65–100) from Flanders-Belgium and identified MMP13 as most promising candidate gene. We identified 6 ultra-rare (≤0.01%) MMP13 missense mutations in 6 patients that were absent from the control cohort. We observed in one control individual a frameshift mutation (p.G269Qfs*2) leading to a premature termination codon. Based on previously described functional evidence, suggesting that MMP13 regulates BACE1 processing, and our genetic findings, we hypothesize a gain-of-function disease mechanism for the missense mutations found in patients. Functional experimental studies remain essential to assess the effect of these mutations on disease related processes and genetic replication studies are needed to corroborate our findings.

Metalloproteinases in Ovarian Cancer.

Proteases play a crucial role in the progression and metastasis of ovarian cancer. Pericellular protein degradation and fragmentation along with remodeling of the extracellular matrix (ECM) is accomplished by numerous proteases that are present in the ovarian tumor microenvironment. Several proteolytic processes have been linked to cancer progression, particularly those facilitated by the matrix metalloproteinase (MMP) family. These proteases have been linked to enhanced migratory ability, extracellular matrix breakdown, and development of support systems for tumors. Several studies have reported the direct involvement of MMPs with ovarian cancer, as well as their mechanisms of action in the tumor microenvironment. MMPs play a key role in upregulating transcription factors, as well as the breakdown of structural proteins like collagen. Proteolytic mechanisms have been shown to enhance the ability of ovarian cancer cells to migrate and adhere to secondary sites allowing for efficient metastasis. Furthermore, angiogenesis for tumor growth and development of metastatic implants is influenced by upregulation of certain proteases, including MMPs. While proteases are produced normally in vivo, they can be upregulated by cancer-associated mutations, tumor–microenvironment interaction, stress-induced catecholamine production, and age-related pathologies. This review outlines the important role of proteases throughout ovarian cancer progression and metastasis.

Role of Gelatinases MMP-2 and MMP-9 in Healthy and Complicated Pregnancy and Their Future Potential as Preeclampsia Biomarkers.

Gelatinases (matrix metalloproteinase-2 and -9) are enzymes from the matrix metalloproteinases (MMPs) family, which are associated with collagen degradation. MMP-2 is capable of cleaving gelatine, types I and IV collagens, while MMP-9 is incapable of direct proteolysis of collagen I and digests collagen type IV. MMP-2 and -9 are both important regulators of vascular and uterine remodeling in a healthy pregnancy. Alterations in the collagen structure of the uterus and spiral arteries are observed in women with hypertensive disorders of pregnancy. Dysregulation of MMP-2 and MMP-9 has been implicated in abnormal vasodilation, placentation, and uterine expansion in preeclampsia. Early preeclampsia detection is paramount for risk stratification and prevention of further complications. Understanding the role of MMP-2 and-9 in uteroplacental and vascular remodeling could help design new approaches for prediction and management of preeclampsia. This review presents a general survey of MMP-2 and MMP-9 faulty regulation and impaired collagen types I and IV turnover in complicated pregnancies. Their potential role as circulating markers for diagnosis, prognosis, and monitoring of preeclampsia development is discussed as well.

Deciphering the genetic alterations in matrix metallo-proteinase gene family and its putative association with head and neck squamous cell carcinoma.

Matrix metallo-proteinases (MMPs) a group of zinc-dependent proteolytic enzymes which play a key role in tumorigenesis by degrading almost all extracellular matrix (ECM) components. MMPs are associated with tumour progression including invasion, angiogenesis, metastasis and poor prognosis. Genetic alterations such as single nucleotide variations and other gross chromosomal abnormalities have been found to drive the process of malignant transformation. In line with the above facts, the present study aims to analyse the genetic alterations, associated gene expression patterns and survival probability of HNSCC patients upon differential expression of the crucial members of the MMP family. The observational study utilised several computational tools. The cBioportal database was used as the primary source of identification of genetic alterations in the MMP family of genes. The Cancer Gene Atlas dataset (Firehose Legacy) was used for the investigations. The highest frequency of alteration was identified in the MMP20 gene (8%). The common gene alterations were amplifications, deep deletions, mis-sense and truncating mutations. Interestingly, amplification and deep deletion followed the same pattern in about 31 patients, in genes MMP1, 3, 7, 8, 10, 12, 20, and 27. The MMP20 gene expression analysis showed a significant difference between the normal subjects and the patients with primary tumors (6.95 x 10-4). The Kaplan-Meier survival curve analysis identified that female patients with high-level expression of the MMP20 gene had a low survival probability when compared to male HNSC patients. Taken together, the present study provides preliminary information about the involvement of the MMP20 gene of the MMP family with HNSCC. Further experimental analysis is required to derive a strong association between the gene alterations observed with HNSCC.

Mechanistic Insights into Side Effects of Troglitazone and Rosiglitazone Using a Novel Inverse Molecular Docking Protocol.

Thiazolidinediones form drugs that treat insulin resistance in type 2 diabetes mellitus. Troglitazone represents the first drug from this family, which was removed from use by the FDA due to its hepatotoxicity. As an alternative, rosiglitazone was developed, but it was under the careful watch of FDA for a long time due to suspicion, that it causes cardiovascular diseases, such as heart failure and stroke. We applied a novel inverse molecular docking protocol to discern the potential protein targets of both drugs. Troglitazone and rosiglitazone were docked into predicted binding sites of >67,000 protein structures from the Protein Data Bank and examined. Several new potential protein targets with successfully docked troglitazone and rosiglitazone were identified. The focus was devoted to human proteins so that existing or new potential side effects could be explained or proposed. Certain targets of troglitazone such as 3-oxo-5-beta-steroid 4-dehydrogenase, neutrophil collagenase, stromelysin-1, and VLCAD were pinpointed, which could explain its hepatoxicity, with additional ones indicating that its application could lead to the treatment/development of cancer. Results for rosiglitazone discerned its interaction with members of the matrix metalloproteinase family, which could lead to cancer and neurodegenerative disorders. The concerning cardiovascular side effects of rosiglitazone could also be explained. We firmly believe that our results deepen the mechanistic understanding of the side effects of both drugs, and potentially with further development and research maybe even help to minimize them. On the other hand, the novel inverse molecular docking protocol on the other hand carries the potential to develop into a standard tool to predict possible cross-interactions of drug candidates potentially leading to adverse side effects.

Antitumor effect and molecular mechanism of fucoidan in NSCLC

BackgroundFucoidan, a water-soluble polysaccharide, exerts anticoagulant and antiviral functions. It was recently reported that fucoidan also exerts an antitumor function. Lung cancer is one of the most common cancers in the world. The aim of this study was to investigate anti-tumor,apoptosis and anti-metastasis effects of fucoidan in both cell-based assays and mouse xenograft model, as well as to clarify possible role of m-TOR pathway in the protection.MethodsIn vitro: Different concentrations of fucoidan were given to act on non-small cell lung cancer (NSCLC) cell lines A549 and H1650. The effects of fucoidan on cell proliferation were observed by detecting cyclin expression levels, CCK8 and EDU experiments and cloning experiments. The apoptotic level was detected by flow cytometry and the apoptotic protein level was detected by Westernblot. By detecting the expression of adhesion molecules, the expression of matrix metalloproteinase (MMP) family, and Transwell cell invasion and migration experiment, the effect of fucoidan on cell adhesion, invasion and migration was observed. Meanwhile the effect of fucoidan on angiogenesis was observed by detecting the expression of vascular endothelial growth factor (VEGF).In vivo experiment: An animal model of NSCLC cell mouse subcutaneous xenograft tumor was established to analyze the correlation between the consumption of fucoidan and the size and volume of xenograft tumor through gross observation. Through immunohistochemical staining and immunofluorescence double staining, ki67 and cell adhesion molecules (E-cadherin, N-cadherin and CD31) and VEGF-A in the tumor were detected, and the correlation between the amount of fucoidan and the above indexes was analyzed.ResultsFucoidan inhibited the proliferation and angiogenesis of NSCLC cells via the mTOR pathway and promoted their apoptosis by increasing the Bax/Bcl-2 ratio. Not only that, fucoidan inhibited NSCLC cell invasion via epithelial–mesenchymal transformation (EMT). The mice fed fucoidan exhibited significant reductions in tumor volumes and weights. These indicators (Ki67, VEGF-A,N-cadherin) were decreased and E-cadherin expression was up-regulated in A549 mice that treated with fucoidan. The results showed that fucoidan inhibited tumor proliferation in vivo by affecting the expression of related proteins.ConclusionFucoidan conveys antitumor effects and our results represent an ideal therapeutic agent for NSCLC.

The matrix metalloproteinase gene family: a significant prognostic gene lineage correlated with immune infiltrates in laryngeal squamous cell carcinoma.

This study aimed to elucidate the potential genes of the matrix metalloproteinase (MMP) family, responsible for the progression of laryngeal squamous cell carcinoma (LSCC). Besides, we ascertained the changes in common malignant behaviors in vitro by knocking down MMP1. TCGA, GEO, Oncomine, and microarray data were conducted to analyze the expression levels of MMPs and to find tissue-specific genes in LSCC. Univariate and multivariate Cox regression analyses were established in the construction of a prognostic model based on expression profiles and clinical information of LSCC in TCGA. We then comprehensively analyzed survival, co-expression network, and immune infiltration based on a prognostic model by Kaplan-Meier analysis, WGCNA, and CIBERSORT. Thereafter, qRT-PCR, proliferation, Transwell, and wound-healing assays were used to assess the accuracy of the bioinformatics data. A total of seven genes in the MMP family were identified as differentially expressed genes (DEGs) by integrating three public databases and microarray data. Additionally, multivariate Cox regression was used to establish a four-gene (MMP1/3/8/10) prognostic model, which exhibited a better predictive accuracy than the TNM (tumors/nodes/metastases) based model. The prognostic model was related to plasma cells, CD8+ T cells, follicular helper T cells, resting NK cells, and M0 macrophages infiltration. The expression of MMP1, MMP3, and MMP10 was the highest in head and neck squamous cell carcinoma (HNSC) compared to other cancer in the Oncomine and GEPIA dataset. Further, MMP1 demonstrated significant upregulation in 40 paired LSCC tissues. Eventually, MMP1 downregulation inhibited cell viability, colony formation, and cell migration in TU686 and FaDu cells. Our findings suggest that the four-gene signature might be associated with the prognosis. Further, we revealed that MMP1 is a pivotal biomarker for the biotherapy and prognostic evaluation of patients with LSCC.

A mini review on the associations of matrix metalloproteinases (MMPs) -1, -8, -13 with periodontal disease

Matrix metalloproteinases (MMPs) are one of the most important endopeptidases in periodontal disease that generally degrade extracellular matrix (ECM) components of periodontal supporting tissues, leading to tooth loss. Among the MMP family, MMP-1, -8 and -13, which are also known as the collagenase group, play a vital role in the degradation of ECM collagen and non-collagen substances. Elevated levels of MMP -1, -8 and -13 are markedly significant within tissue, gingival crevicular fluid (GCF), and saliva of patients with periodontitis, which help to explain the progression pattern of the disease. This review provides an overview of MMP -1, -8, and -13 on their structures, functions and their critical role in periodontitis.

Immunohistochemical Expression of MMP-2 in Pancreatic Carcinoma and Chronic Pancreatitis

<i>Introduction:</i> Matrix metalloproteinase (MMP)-2 is a member of MMPs family which is zinc-dependent endopeptidases that degrade all components of ECM and vascular basement membrane. MMPs are closely involved in tumor invasion and metastasis. <i>Aim of the work:</i> is to evaluate the immune-expression and clinical significance of MMPs molecule in patients with pancreatic carcinoma. <i>Materials and Methods:</i> A total of 25 pancreatic carcinomas were evaluated for expression of MMP-2 by immunohistochemical technique. The expression was evaluated. The study included 24/25 cases of PDAC and 1/25 acinar cell carcinoma. PDAC included 5/24 cases of well differentiated, 16/24 cases of moderately differentiated, 3/24 cases of poorly differentiated adenocarcinoma. <i>Results:</i> Pancreatic carcinoma specimens showed positive cytoplasmic MMP-2 staining with high expression in 88% of studied specimens as their IRS ranged from 6/9 to 9/9 with high extent and intensity. There was a statistically significant relationship between MMP-2 expression and high grade in PDAC (p<0.024). <i>Conclusion:</i> MMP-2 was expressed in PDAC and not in pancreatitis cases. The expression of MMP-2 was correlated with high histological grade and poor prognosis in PDAC.