Periostin Directly and Indirectly Promotes Tumor Lymphangiogenesis of Head and Neck Cancer 英文参考文献.docVIP

PeriostinDirectlyandIndirectlyPromotesTumor LymphangiogenesisofHeadandNeckCancer YasuseiKudo1,6*,ShinjiIizuka1,MakiYoshida1,PhuongThaoNguyen1,SamadaraniB.S.M.Siriwardena1, TakaakiTsunematsu1,MarikoOhbayashi1,ToshinoriAndo1,DaijiroHatakeyama2,ToshiyukiShibata2, KeiichiKoizumi3,MasahiroMaeda4,NaozumiIshimaru6,IkukoOgawa5,TakashiTakata1* 1Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan, 2Department of Oral and MaxillofacialSciences,GifuUniversityGraduateSchoolofMedicine,Gifu,Japan,3DepartmentofKampoDiagnostic,InstituteofNaturalMedicine,UniversityofToyama, Toyama,Japan,4DepartmentofResearchandDevelopment,Immuno-BiologicalLaboratories,Co.,Ltd.,Fujioka-shi,Gunma,Japan,5CenterofOralClinicalExamination, HiroshimaUniversityHospital,Hiroshima,Japan,6DepartmentofOralMolecularPathology,InstituteofHealthBiosciences,TheUniversityofTokushimaGraduateSchool, Tokushima,Japan Abstract Background: Metastasis to regional lymph nodes via lymphatic vessels plays a key role in cancer progression. Tumor lymphangiogenesis is known to promote lymphatic metastasis, and vascular endothelial growth factor C (VEGF-C) is a critical activator of tumor lymphangiogenesis during the process of metastasis. We previously identified periostin as an invasion- and angiogenesis-promoting factor in head and neck squamous cell carcinoma (HNSCC). In this study, we discoveredanovelroleforperiostinintumorlymphangiogenesis. Methods and Findings: Periostin overexpression upregulated VEGF-C mRNA expression in HNSCC cells. By using conditionedmediafromperiostin-overexpressingHNSCCcells,weexaminedtubeformationoflymphaticendothelialcells. Conditioned media from periostin-overexpressing cells promoted tube formation. To know the correlation between periostin and VEGF-C, we compared Periostin expression with VEGF-C expression in 54 HNSCC cases by immunohisto- chemistry.PeriostinexpressionwascorrelatedwellwithVEGF-CexpressioninHNSCCcases.