Pancreatic Cancer Cells Enhance the Ability of Collagen Internalization during Epithelial–Mesenchymal Transition 英文参考文献.docVIP

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Pancreatic Cancer Cells Enhance the Ability of Collagen Internalization during Epithelial–Mesenchymal Transition 英文参考文献.doc

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Pancreatic Cancer Cells Enhance the Ability of Collagen Internalization during Epithelial–Mesenchymal Transition 英文参考文献

PancreaticCancerCellsEnhancetheAbilityofCollagen InternalizationduringEpithelial–Mesenchymal Transition NaokiIkenaga1,2,KenokiOhuchida1,3*,KazuhiroMizumoto1,4*,ShinAkagawa1,KenjiFujiwara1, DaikiEguchi1,ShingoKozono1,TakaoOhtsuka1,ShunichiTakahata1,MasaoTanaka1 1Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 2Research Fellow of the Japan Society for the PromotionofScience,Tokyo,Japan,3DepartmentofAdvancedMedicalInitiatives,GraduateSchoolofMedicalSciences,KyushuUniversity,Fukuoka,Japan,4Kyushu UniversityHospitalCancerCenter,Fukuoka,Japan Abstract Background: Extracellular matrix (ECM) remodeling is predominantly mediated by fibroblasts using intracellular and extracellular pathways. Although it is well known that extracellular degradation of the ECM by proteases derived from cancer cells facilitates cellular invasion, the intracellular degradation of ECM components by cancer cells has not been clarified. The aim of this study was to characterize collagen internalization, which is the initial step of the intracellular degradationpathwayinpancreaticcancercells,inlightofepithelial–mesenchymaltransition(EMT). Methodology/PrincipalFindings:Weanalyzedthefunctionofcollageninternalizationintwopancreaticcancercelllines, SUIT-2andKP-2,andpancreaticstellatecells(PSCs)usingOregonGreen488-gelatin.PSCshadastrongabilityforcollagen uptake, and the pancreatic cancer cells also internalized collagen although less efficiently. The collagen internalization abilitiesofSUIT-2andKP-2cellswerepromotedbyEMTinducedbyhumanrecombinanttransforminggrowthfactorb1 (P,0.05). Expression of Endo180, a collagen uptake receptor, was high in mesenchymal pancreatic cancer cell lines, as determined by EMT marker expression (P,0.01). Quantitative RT-PCR and western blot analyses showed that Endo180 expression was also increased by EMT induction in SUIT-2 and KP-2 cells. Endo180 knockdown by RNA interference attenuatedthecollagenuptake(P,0.01)andinv