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RESEARCH PRODUCT

MMP-10/stromelysin-2 promotes invasion of head and neck cancer.

Hirotaka TaniSamadarani B. S. M. SiriwardenaShinji IizukaTakashi TakataMohammad Reza KiekhaeeMaki YoshidaYasusei KudoElsayed Mohamed DerazMariko ObayashiLorenzo Lo MuzioTakaaki TsunematsuYoshimitsu AbikoAkira KikuchiGuangying QiIkuko OgawaGiuseppina Campisi

subject

Tumor PhysiologyClone (cell biology)p38 Mitogen-Activated Protein KinasesMetastasisMetastasisMolecular Cell BiologyBasic Cancer ResearchNeoplasm MetastasisRegulation of gene expressionGene knockdownMultidisciplinaryHead and Neck cancerQRTransfectionHead and Neck TumorsExtracellular MatrixUp-RegulationGene Expression Regulation NeoplasticOncologyHead and Neck NeoplasmsGene Knockdown TechniquesCarcinoma Squamous CellMedicineResearch ArticleScience490Oral MedicineBiologyPeriostinHead and Neck Squamous Cell CarcinomaMatrix Metalloproteinase 10stomatognathic systemSettore MED/28 - Malattie OdontostomatologicheCell Line TumormedicineCancer Detection and Diagnosisotorhinolaryngologic diseasesHumansNeoplasm Invasiveness490BiologyExtracellular Matrix AdhesionsProtein Kinase InhibitorsneoplasmsMicroarray analysis techniquesCancers and Neoplasmsmedicine.diseaseMolecular biologyHead and neck squamous-cell carcinomaAntigens DifferentiationWnt Proteinsstomatognathic diseasesCancer researchCell Adhesion Molecules

description

BackgroundPeriostin, IFN-induced transmembrane protein 1 (IFITM1) and Wingless-type MMTV integration site family, member 5B (Wnt-5b) were previously identified as the invasion promoted genes of head and neck squamous cell carcinoma (HNSCC) by comparing the gene expression profiles between parent and a highly invasive clone. We have previously reported that Periostin and IFITM1 promoted the invasion of HNSCC cells. Here we demonstrated that Wnt-5b overexpression promoted the invasion of HNSCC cells. Moreover, stromelysin-2 (matrix metalloproteinase-10; MMP-10) was identified as a common up-regulated gene among Periostin, IFITM1 and Wnt-5b overexpressing HNSCC cells by using microarray data sets. In this study, we investigated the roles of MMP-10 in the invasion of HNSCC.Methods and findingsWe examined the expression of MMP-10 in HNSCC cases by immunohistochemistry. High expression of MMP-10 was frequently observed and was significantly correlated with the invasiveness and metastasis in HNSCC cases. Next, we examined the roles of MMP-10 in the invasion of HNSCC cells in vitro. Ectopic overexpression of MMP-10 promoted the invasion of HNSCC cells, and knockdown of MMP-10 suppressed the invasion of HNSCC cells. Moreover, MMP-10 knockdown suppressed Periostin and Wnt-5b-promoted invasion. Interestingly, MMP-10 overexpression induced the decreased p38 activity and MMP-10 knockdown induced the increased p38 activity. In addition, treatment with a p38 inhibitor SB203580 in HNSCC cells inhibited the invasion.ConclusionsThese results suggest that MMP-10 plays an important role in the invasion and metastasis of HNSCC, and that invasion driven by MMP-10 is partially associated with p38 MAPK inhibition. We suggest that MMP-10 can be used as a marker for prediction of metastasis in HNSCC.

10.1371/journal.pone.0025438https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21998657/pdf/?tool=EBI