Invadopodia proteins, cortactin, N-WASP and WIP differentially promote local invasiveness in ameloblastoma

• Published in: Journal of oral pathology & medicine 2016-09, Vol.45 (8), p.591-598
• Main Authors: Siar, Chong Huat, Rahman, Zainal Ariff Bin Abdul, Tsujigiwa, Hidetsugu, Mohamed Om Alblazi, Kamila, Nagatsuka, Hitoshi, Ng, Kok Han
• Format: Article
• Language: English
• Subjects: Actins - analysis; Actins - biosynthesis; Actins - physiology; Adolescent; Adult; Aged; ameloblastoma; Ameloblastoma - metabolism; Ameloblastoma - pathology; Cell Movement - physiology; Child; cortactin; Cortactin - biosynthesis; Cortactin - physiology; Cytoskeletal Proteins - biosynthesis; Cytoskeletal Proteins - physiology; Dentistry; Female; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins - biosynthesis; Intracellular Signaling Peptides and Proteins - physiology; Jaw Neoplasms - metabolism; Jaw Neoplasms - pathology; Male; Middle Aged; N-WASP; Neoplasm Invasiveness; Neoplasms, Glandular and Epithelial - metabolism; Podosomes - physiology; src-Family Kinases - analysis; src-Family Kinases - physiology; Stromal Cells - metabolism; Stromal Cells - pathology; WIP; Wiskott-Aldrich Syndrome Protein, Neuronal - biosynthesis; Wiskott-Aldrich Syndrome Protein, Neuronal - physiology; Young Adult
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1111/jop.12417

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. Materials and method 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.