title: Matrigel induces L-plastin expression and promotes L-plastin-dependent invasion in human cholangiocarcinoma cells.
abstract: The function of the extracellular matrix (ECM) in the tumor microenvironment is not limited to forming a barrier against tumor invasion. As demonstrated in pathological specimens, cholangiocarcinoma samples exhibit an enrichment of the ECM surrounding the tumor cells. In this study, we examined involvement of the ECM in the regulation of the invasiveness of cholangiocarcinoma cells. The RMCCA1 cholangiocarcinoma cell line was cultured in culture plates either with or without a coating of reconstituted ECM basement membrane preparation (BD Matrigel matrix).In vitroinvasion assays were then performed. In addition, the protein expression profile of the cell line was examined using two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry. The proteins expressed and their functional associations with cancer progression were determined. Culturing the RMCCA1 cell line in the BD Matrigel matrix induced cell invasion. Numerous proteins were induced by culturing the RMCCA1 cells in the matrix gel. The expression of L-plastin, an actin-binding protein, was significantly upregulated. The knockdown of L-plastin expression by siRNA silencing significantly suppressed the cellular response to matrix gel-stimulated cancer cell invasion. The ECM promotes the invasiveness of cholangiocarcinoma cells by upregulating L-plastin. These findings suggest the potential exploitation of this mechanism as a means of inhibiting the invasiveness of cholangiocarcinoma cells.
authors.affiliation: Inter-Departmental Program in Biomedical Sciences, Faculty of the Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Suthidarak
authors.initials: S
authors.lastname: Chaijan
authors.affiliation: The National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumtani 12120, Thailand.
authors.forename: Sittiruk
authors.initials: S
authors.lastname: Roytrakul
authors.affiliation: Center for Excellence in the Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Apiwat
authors.initials: A
authors.lastname: Mutirangura
authors.affiliation: Department of Surgery, Rajavithi Hospital, Bangkok 10400, Thailand.
authors.forename: Kawin
authors.initials: K
authors.lastname: Leelawat
keywords: L-plastin; cancer cell invasion; cholangiocarcinoma; extracellular matrix; liquid chromatography-tandem mass spectrometry