title: Dermatopontin: a potential predictor for metastasis of human oral cancer.
abstract: Dermatopontin (DPT), a component of the extracellular matrix (ECM), is involved in promotion of cellular adhesion and ECM assembly activities. However, the role of DPT in the pathogenesis of carcinoma is unclear. We evaluated DPT expression in human oral cancer and its possible roles including cellular adhesion and invasiveness. We first investigated the DPT mRNA and protein expression status in human oral squamous cell carcinoma (OSCC)-derived cells. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunoblotting analysis detected frequent downregulation of DPT in OSCC-derived cells compared to human normal oral keratinocytes. To assess the epigenetic regulation of DPT, OSCC-derived cells were treated with a histone deacetylase inhibitor, sodium butyrate (NaB). NaB restored the DPT expression in OSCC-derived cells. DPT-overexpressed cells were examined whether DPT could contribute to cellular adhesion and invasiveness. Markedly, increased adhesion and decreased invasiveness in DPT-overexpressed cells were found compared to mock-transfected cells. Adhesion of DPT-overexpressed cells was inhibited by α3β1 integrin functional blocking antibody. OSCC-derived cells treated with NaB also decreased invasiveness. The expression status of DPT in primary OSCCs (n = 97) was analyzed and compared to clinicopathological behavior. DPT expression in primary OSCCs was significantly lower (p < 0.05) than in the normal counterparts and was correlated significantly (p < 0.05) with regional lymph node metastasis. Our data provided strong evidence that downregulation of DPT is a characteristic event in OSCCs and that DPT was correlated with cellular adhesion and invasiveness. Therefore, DPT might play an important role in regulating tumor invasion and metastasis.
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamatoji
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kasamatsu
authors.forename: Yukinao
authors.initials: Y
authors.lastname: Kouzu
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Koike
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ogawara
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiiba
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019138:Antibodies, Blocking; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D039201:Integrin alpha3beta1 / Q000276:immunology; D015603:Keratinocytes / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D019138:Antibodies, Blocking; D002087:Butyrates; D011508:Chondroitin Sulfate Proteoglycans; C082019:DPT protein, human; D016326:Extracellular Matrix Proteins; D056572:Histone Deacetylase Inhibitors; D039201:Integrin alpha3beta1; D012333:RNA, Messenger; D020148:Butyric Acid