title: Loss of cell invasiveness through PKC-mediated syndecan-1 downregulation in melanoma cells under anchorage independency.
abstract: Anchorage-independent survival is one of the key features for malignant tumor cells. Whether specific gene alterations contributed by anchorage independency would further affect metastatic phenotypes of melanoma cells was unclear. We adapted suspension culture of melanoma cells to establish anchorage independency. The suspended melanoma cells lost their invasive abilities in vitro. Specific loss of laminin-binding ability in suspended melanoma cells was observed, which was correlated with downregulation of syndecan-1 as revealed by microarray and validated by qPCR and Western blot. Modulation of syndecan-1 expression level affected laminin binding, transwell migration and matrix metalloproteinase-2 secretion in melanoma cells. SDC1 expression and transwell migration were correlated with activity or level of protein kinase Cδ as evidence by specific inhibitors and shRNA transfection. In this study, we compared metastatic phenotypes and gene expressions of adherent and suspended melanoma cells. The anchorage independency led to protein kinase Cδ-mediated syndecan-1 downregulation, which contributed to loss of laminin-binding ability, reduced metalloproteinase-2 secretion and loss of invasiveness.
authors.affiliation: School of Medicine, FuJen Catholic University, New Taipei City, Taiwan; Department of Dermatology, Cardinal Tien Hospital, New Taipei City, Taiwan.
authors.forename: ChiaChen
authors.initials: C
authors.lastname: Wang
authors.forename: TingTing
authors.initials: T
authors.lastname: Tseng
authors.forename: Yaoyun
authors.initials: Y
authors.lastname: Jhang
authors.forename: JenChih
authors.initials: J
authors.lastname: Tseng
authors.forename: ChiaoHui
authors.initials: C
authors.lastname: Hsieh
authors.forename: Wen-guey
authors.initials: WG
authors.lastname: Wu
authors.forename: ShaoChen
authors.initials: S
authors.lastname: Lee
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype; D051745:Protein Kinase C-delta / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*; D053668:Syndecan-1 / Q000378:metabolism*
chemical_list: D007797:Laminin; D034741:RNA, Small Interfering; C508241:SDC1 protein, human; D053668:Syndecan-1; D051745:Protein Kinase C-delta; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: anchorage independency; laminin; melanoma; protein kinase C; syndecan