title: MMP-10/stromelysin-2 promotes invasion of head and neck cancer.
abstract: BACKGROUND
  Periostin, 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  These 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.
authors: Division of Frontier Medical Science, Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors: Elsayed Mohamed
authors: EM
authors: Deraz
authors: Yasusei
authors: Y
authors: Kudo
authors: Maki
authors: M
authors: Yoshida
authors: Mariko
authors: M
authors: Obayashi
authors: Takaaki
authors: T
authors: Tsunematsu
authors: Hirotaka
authors: H
authors: Tani
authors: Samadarani B S M
authors: SB
authors: Siriwardena
authors: Mohammad Reza
authors: MR
authors: Keikhaee
authors: Mohammad Reza
authors: MR
authors: Kiekhaee
authors: Guangying
authors: G
authors: Qi
authors: Shinji
authors: S
authors: Iizuka
authors: Ikuko
authors: I
authors: Ogawa
authors: Giuseppina
authors: G
authors: Campisi
authors: Lorenzo
authors: L
authors: Lo Muzio
authors: Yoshimitsu
authors: Y
authors: Abiko
authors: Akira
authors: A
authors: Kikuchi
authors: Takashi
authors: T
authors: Takata
mesh_terms: D000943:Antigens, Differentiation / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053506:Matrix Metalloproteinase 10 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D051153:Wnt Proteins / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D047428:Protein Kinase Inhibitors; C435831:WNT5B protein, human; D051153:Wnt Proteins; C062010:leu-13 antigen; D048051:p38 Mitogen-Activated Protein Kinases; D053506:Matrix Metalloproteinase 10