A novel and selective membrane type-1 matrix metalloproteinase (MT1-MMP) inhibitor reduces cancer cell motility and tumor growth

Suojanen, Juho; Salo, Tuula; Koivunen, Erkki; Sorsa, Timo; Pirilä, Emma

doi:10.4161/cbt.8.24.10139

Cited by 43 publications

(24 citation statements)

References 38 publications

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“…PLAU and MMP14 are proteases which promote tumor invasiveness and metastasis through their involvement in the degradation of the extracellular matrix. They have been previously implicated in HNC as well as other tumor types, and their inhibition has been explored for therapeutic purposes (17,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47). IGFBP7 is a tumor suppressor protein shown to be down-regulated in solid tumors of the liver, lung, breast, prostate, colon, and skin (48 -50).…”

Section: Discussionmentioning

confidence: 99%

Potentially Novel Candidate Biomarkers for Head and Neck Squamous Cell Carcinoma Identified Using an Integrated Cell Line-based Discovery Strategy

Sepiashvili

Hui

Ignatchenko

et al. 2012

Molecular & Cellular Proteomics

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Head and neck squamous cell carcinomas (HNSCC) can arise from the oral cavity, oropharynx, larynx or hypopharynx, and is the sixth leading cancer by incidence worldwide. The 5-year survival rate of HNSCC patients remains static at 40 -60%. Hence, biomarkers which can improve detection of HNSCC or early recurrences should improve clinical outcome. Mass spectrometry-based proteomics methods have emerged as promising approaches for biomarker discovery. As one approach, mass-spectrometric identification of proteins shed or secreted from cancer cells can contribute to the identification of potential biomarkers for HNSCC and our understanding of tumor behavior. In the current study, mass spectrometry-based proteomic profiling was performed on the conditioned media (i.e. secretome) of head and neck cancer (HNC) cell lines (FaDu, UTSCC8 and UTSCC42a) in addition to gene expression microarrays to identify over-expressed transcripts in the HNSCC cells in comparison to a normal control cell line. This integrated data set was systematically mined using publicly available resources (Human Protein Atlas and published proteomic/transcriptomic data) to prioritize putative candidates for validation. Subsequently, quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC), and ELISAs were performed to verify selected markers. Our integrated analyses identified 90 putative protein biomarkers that were secreted or shed to the extracellular space and over-expressed in HNSCC cell lines, relative to controls. Subsequently, the over-expression of five markers was verified in vitro at the transcriptional and translational levels using qRT-PCR and Western blotting, respectively. IHC-based validation conducted in two independent Head and Neck Squamous Cell Carcinoma (HNSCC)1 is the sixth most common cancer worldwide, with ϳ600,000 new cases diagnosed every year (1). HNSCCs include squamous cell carcinomas (SCCs) of the oral cavity, pharynx (nasopharynx, oropharynx, and hypopharynx), and larynx. Despite improvements in therapeutic approaches, the overall 5-year survival rate of HNSCC patients has not improved over the past three decades (1, 2).Clinical management of HNSCC is faced by several challenges, including early detection of the primary tumor, and site-specific control of the disease (3, 4). Early diagnosis is often hampered by the asymptomatic nature of HNSCC development and the inadequacy of current diagnostic methods to identify HNSCCs with sufficient specificity and sensitivity. As a result, over 60% of HNSCC patients present with advanced stages III or IV, harboring lymph node metastases (3).

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Section: Discussionmentioning

confidence: 99%

Potentially Novel Candidate Biomarkers for Head and Neck Squamous Cell Carcinoma Identified Using an Integrated Cell Line-based Discovery Strategy

Sepiashvili

Hui

Ignatchenko

et al. 2012

Molecular & Cellular Proteomics

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“…However, the roles of different MMPs in normal physiology are also significant which cause problems with side significant side effects and for this reason the clinical applications are still to be awaited [22]. For this reason several selective spectrum MMP inhibitors and diagnostic tools have been also designed to target distinct MMPs, especially gelatinases, in oral car cinomas [22][23][24][25]. Interestingly, in intraosseous carcinomas the role of MMPs is considerably less clear which may also relate to its embryonic origins similar to dentigerous cysts.…”

Section: Discussionmentioning

confidence: 99%

Common Matrix Metalloproteinases ( M MP - 8, -9, -25, and -26) Cannot Explain Dentigerous Cyst Expansion

Suojanen¹,

Lehtonen²,

Färkkilä

et al. 2014

JCDR

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“…For example, peptide-based MMPIs interact with secondary binding sites on MMPs and thereby have greater selectivity [40]. Also, phage display peptide libraries have been used to identify selective MMP-2, MMP-9 and MT1-MMP inhibitors that are effective in vivo [41,42]. …”

Section: Introductionmentioning

confidence: 99%

Zymography as a Research Tool in the Study of Matrix Metalloproteinase Inhibitors

Ren

Chen

Khalil

2017

Methods in Molecular Biology

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Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade various components of the extracellular matrix (ECM) and play a role in tissue remodeling. Changes in MMPs have been observed in cancer, connective tissue disorders and vascular disease, and both endogenous tissue inhibitors of MMPs (TIMPs) and synthetic MMP inhibitors (MMPIs) have been evaluated as modulators of MMP activity in various biological systems. Zymography is a simple technique that is commonly used to assess MMP activity and the efficacy of MMPIs. Also, reverse zymography is a modified technique to study the activity of endogenous TIMPs. However, problems are often encountered during the zymography procedure, which could interfere with accurate assessment of MMP activity in control specimens, and thus make it difficult to determine the pathological changes in MMPs and their responsiveness to MMPIs. Simplified protocols for preparation of experimental solutions, tissue preparation, regular and reverse zymography procedures, and zymogram analysis are presented. Additional helpful tips to troubleshoot problems in the zymography technique and to enhance the quality of the zymograms should make it more feasible to determine the changes in MMPs and assess the efficacy of MMPIs in modulating MMP activity in various biological systems and pathological conditions.

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A novel and selective membrane type-1 matrix metalloproteinase (MT1-MMP) inhibitor reduces cancer cell motility and tumor growth

Cited by 43 publications

References 38 publications

Potentially Novel Candidate Biomarkers for Head and Neck Squamous Cell Carcinoma Identified Using an Integrated Cell Line-based Discovery Strategy

Potentially Novel Candidate Biomarkers for Head and Neck Squamous Cell Carcinoma Identified Using an Integrated Cell Line-based Discovery Strategy

Common Matrix Metalloproteinases ( M MP - 8, -9, -25, and -26) Cannot Explain Dentigerous Cyst Expansion

Zymography as a Research Tool in the Study of Matrix Metalloproteinase Inhibitors

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