A Role for Fibrillar Collagen Deposition and the Collagen Internalization Receptor Endo180 in Glioma Invasion 英文参考文献.docVIP
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A Role for Fibrillar Collagen Deposition and the Collagen Internalization Receptor Endo180 in Glioma Invasion 英文参考文献
ARoleforFibrillarCollagenDepositionandtheCollagen
InternalizationReceptorEndo180inGliomaInvasion
IvoJ.Huijbers1,MarjanIravani1,SergeyPopov2,DavidRobertson1,SafaAl-Sarraj3,ChrisJones2,ClareM.
Isacke1*
1BreakthroughBreastCancerResearchCentre,TheInstituteofCancerResearch,London,UnitedKingdom,2PaediatricOncology,TheInstituteofCancerResearch/Royal
MarsdenNHSTrust,Sutton,UnitedKingdom,3ClinicalNeuropathology,King’sCollegeHospital,London,UnitedKingdom
Abstract
Background:Glioblastomamultiforme(GBM,WHOgradeIV)isthemostcommonandmostmalignantofastrocyticbrain
tumors,andisassociatedwithrapidinvasionintoneighboringtissue.Inothertumortypesitiswellestablishedthatsuch
invasioninvolvesacomplexinteractionbetweentumorcellsandlocallyproducedextracellularmatrix.InGBMs,surprisingly
littleisknownabouttheassociatedmatrixcomponents,inparticularthefibrillarproteinssuchascollagensthatareknown
toplayakeyroleintheinvasionofothertumortypes.
Methodology/PrincipalFindings:InthisstudywehaveusedboththeMasson’strichromestainingandahighresolution
multipleimmunofluorescencelabelingmethodtodemonstratethatintratumoralfibrillarcollagensareanintegralpartof
theextracellularmatrixinasubsetofGBMs.Correlatedwiththiscollagendepositionweobservedhighlevelexpressionof
the collagen-binding receptor Endo180 (CD280) in the tumor cells. Further, interrogation of multiple expression array
datasets identified Endo180 as one of the most highly upregulated transcripts in grade IV GBMs compared to grade III
gliomas.Usingpromoteranalysisstudiesweshowthatthisincreasedexpressionis,inpart,mediatedviaTGF-bsignaling.
Functionally, we demonstrate that Endo180 serves as the major collagen internalization receptor in GBM cell lines and
providethefirstevidencethatthisactivityiscriticalfortheinvasionofGBMcellsthroughfibrillarcollagenmatrices.
Conclusions/Significance: This study demonstrates, for the first time, that fibrillar collagensare extensively depositedin
GBMsandthatthecollageninternalizationreceptorEndo180isbothhighlyexpres
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