Differences in the Nemosis Response of Normal and Cancer-Associated Fibroblasts from Patients with Oral Squamous Cell Carcinoma 英文参考文献.docVIP

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Differences in the Nemosis Response of Normal and Cancer-Associated Fibroblasts from Patients with Oral Squamous Cell Carcinoma 英文参考文献.doc

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Differences in the Nemosis Response of Normal and Cancer-Associated Fibroblasts from Patients with Oral Squamous Cell Carcinoma 英文参考文献

DifferencesintheNemosisResponseofNormaland Cancer-AssociatedFibroblastsfromPatientswithOral SquamousCellCarcinoma KatiRa¨sa¨nen1*,IsmoVirtanen2,PertteliSalmenpera¨1,ReidarGrenman3,AnttiVaheri1 1Haartman Institute, University of Helsinki, Helsinki, Finland, 2Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland, 3Department of Otorhinolaryngology-HeadandNeckSurgery,TurkuUniversityCentralHospital,Turku,Finland Abstract Background: Tumor-stroma reaction is associated with activation of fibroblasts. Nemosis is a novel type of fibroblast activation.Itleadstoanincreasedproductionofgrowthfactorsandproinflammatoryandproteolyticproteins,whileatthe same time cytoskeletal proteins are degraded. Here we used paired normal skin fibroblasts and cancer-associated fibroblasts(CAF)andprimaryandrecurrentoralsquamouscellcarcinoma(SCC)cellstostudythenemosisresponse. Principal Findings: Fibroblast nemosis was analyzed by protein and gene expression and the paracrine regulation with colonyformationassay.Oneofthenormalfibroblaststrains,FB-43,upregulatedCOX-2innemosis,butFB-74cellsdidnot. In contrast, CAF-74 spheroids expressed COX-2 but CAF-43 cells did not.Alpha-SMA protein wasexpressed in both CAF strainsandinFB-74cells,butnotinFB-43fibroblasts.ItsmRNAlevelsweredownregulatedinnemosis,buttheCAFsstarted to regain the expression. FSP1 mRNA was downregulated in normal fibroblasts and CAF-74 cells, but not in CAF-43 fibroblasts.SerineproteaseFAPwasupregulatedinallfibroblasts,moresoinnemoticCAFs.VEGF,HGF/SFandFGF7mRNA levelswereupregulatedtovariabledegreeinnemosis.CAFsincreasedthecolonyformationofprimarytumorcelllinesUT- SCC-43A and UT-SCC-74A, but normal fibroblasts inhibited the anchorage-independent growth of recurrent UT-SCC-43B andUT-SCC-74Bcells. Conclusions:Nemosisresponse,asobservedbyCOX-2andgrowthfactorinduction,andexpressionofCAFmarkersa-SMA, FSP1andFAP,variesbetweenfibroblastpopulations.TheexpressionofCAFmarkersdiffersbetweennormalfibroblastsand CAFsinnemo