title: Invadopodia proteins, cortactin, N-WASP and WIP differentially promote local invasiveness in ameloblastoma.
abstract: BACKGROUND
  Cell migration and invasion through interstitial tissues are dependent upon several specialized characteristics of the migratory cell notably generation of proteolytic membranous protrusions or invadopodia. Ameloblastoma is a benign odontogenic epithelial neoplasm with a locally infiltrative behaviour. Cortactin and MMT1-MMP are two invadopodia proteins implicated in its local invasiveness. Other invadopodia regulators, namely N-WASP, WIP and Src kinase remain unclarified. This study addresses their roles in ameloblastoma.
  
  
  METHODS
  Eighty-seven paraffin-embedded ameloblastoma cases (20 unicystic, 47 solid/multicystic, 3 desmoplastic and 17 recurrent) were subjected to immunohistochemistry for expression of cortactin, N-WASP, WIP, Src kinase and F-actin, and findings correlated with clinicopathological parameters.
  
  
  RESULTS
  Invadopodia proteins (except Src kinase) and F-actin were widely detected in ameloblastoma (cortactin: n = 73/87, 83.9%; N-WASP: n = 59/87; 67.8%; WIP: n = 77/87; 88.5%; and F-actin: n = 87/87, 100%). Protein localization was mainly cytoplasmic and/or membranous, and occasionally nuclear for F-actin. Cortactin, which functions as an actin-scaffolding protein, demonstrated significantly higher expression levels within ameloblastoma tumoral epithelium than in stroma (P < 0.05). N-WASP, which coordinates actin polymerization and invadopodia-mediated extracellular matrix degradation, was overexpressed in the solid/multicystic subtype (P < 0.05). WIP, an upstream regulator of N-WASP, and F-actin were significantly upregulated along the tumour invasive front compared to tumour centres (P < 0.05). Except for males with cortactin overexpression, other clinical parameters (age, ethnicity and anatomical site) showed no significant correlations.
  
  
  CONCLUSIONS
  Present results suggest that local invasiveness of ameloblastoma is dependent upon the migratory potential of its tumour cells as defined by their distribution of cortactin, N-WASP and WIP in correlation with F-actin cytoskeletal dynamics.
authors.affiliation: Department of Oro-Maxillofacial Surgical and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Chong Huat
authors.initials: CH
authors.lastname: Siar
authors.affiliation: Department of Oro-Maxillofacial Surgical and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Zainal Ariff Bin Abdul
authors.initials: ZA
authors.lastname: Rahman
authors.affiliation: Laboratory of Histopathology, Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Tsujigiwa
authors.affiliation: Department of Oro-Maxillofacial Surgical and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kamila
authors.initials: K
authors.lastname: Mohamed Om Alblazi
authors.affiliation: Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagatsuka
authors.affiliation: Unit of Stomatology, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: Kok Han
authors.initials: KH
authors.lastname: Ng
mesh_terms: D000199:Actins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000564:Ameloblastoma / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D002648:Child; D051356:Cortactin / Q000096:biosynthesis / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000502:physiology*; D007573:Jaw Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism; D000069261:Podosomes / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000096:biosynthesis / Q000502:physiology*; D055815:Young Adult; D019061:src-Family Kinases / Q000032:analysis / Q000502:physiology
chemical_list: D000199:Actins; D051356:Cortactin; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C495771:WASL protein, human; C109903:WIPF1 protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D019061:src-Family Kinases
keywords: N-WASP; WIP; ameloblastoma; cortactin