Bone Marrow Suppression by c-Kit Blockade Enhances Tumor Growth of Colorectal Metastases through the Action of Stromal Cell-Derived Factor-1英文文献资料.docVIP

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Bone Marrow Suppression by c-Kit Blockade Enhances Tumor Growth of Colorectal Metastases through the Action of Stromal Cell-Derived Factor-1英文文献资料.doc

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Bone Marrow Suppression by c-Kit Blockade Enhances Tumor Growth of Colorectal Metastases through the Action of Stromal Cell-Derived Factor-1英文文献资料

HindawiPublishingCorporation JournalofOncology Volume2012,ArticleID196957,12pages doi:10.1155/2012/196957 ResearchArticle BoneMarrowSuppressionbyc-KitBlockadeEnhancesTumor GrowthofColorectalMetastasesthroughtheActionofStromal Cell-DerivedFactor-1 ClaudiaScheuer, MichaelD.Menger, KathrinRupertus,1,2GudrunC.Y.Haberl,1 3 3 1 1 MartinK.Schilling, andOttoKollmar 1 2 3 DepartmentofGeneral,Visceral,VascularandPediatricSurgery,UniversityofSaarland,66421Homburg,Germany DepartmentofHematology,OncologyandImmunology,UniversityofT¨ubingen,72074T¨ubingen,Germany InstituteforClinicalandExperimentalSurgery,UniversityofSaarland,66421Homburg,Germany CorrespondenceshouldbeaddressedtoOttoKollmar,otto.kollmar@uniklinikum-saarland.de Received1June2011;Revised2August2011;Accepted7August2011 AcademicEditor:DebabrataMukhopadhyay Copyright?2012KathrinRupertusetal. This is an open access article distributed under the Creative Commons Attribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. Background. Mobilization of c-Kit hematopoietic cells (HCs) contributes to tumor vascularization. Whereas survival and + proliferationofHCsareregulatedbybindingofthestemcellfactortoitsreceptorc-Kit,migrationofHCsisdirectedbystromal cell-derived factor (SDF)-1. Therefore, targeting migration of HCs provides a promising new strategy of anti-tumor therapy. Methods.BALB/cmice(n=16)werepretreatedwithananti-c-KitantibodyfollowedbyimplantationofCT26.WT-GFPcolorectal cancercellsintodorsalskinfoldchambers.Animals(n = 8)additionallyreceivedaneutralizinganti-SDF-1antibody.Animals (n=8)treatedwithacontrolantibodyservedascontrols.Investigationswereperformedusingintravital?uorescencemicroscopy, immunohistochemistry,?owcytometryandwesternblotanalysis.Results.Blockadeofc-Kitsigni?cantlyenhancedtumorcell engraftmentcomparedtocontrolsduetostimulationoftumorcellproliferationandinvasionwith