Chemokine Receptors in Cancer PDF
Preview Chemokine Receptors in Cancer
CANCER DRUG DISCOVERY AND DEVELOPMENT Chemokine Receptors in Cancer Edited by Amy M. Fulton Cancer Drug Discovery and Development Series Editor: Beverly A. Teicher Forothertitlespublishedinthisseries,goto http://www.springer.com/series/7625 Amy M. Fulton Editor Chemokine Receptors in Cancer Editor AmyM.Fulton DepartmentofPathology SchoolofMedicine MarleneandStewart GreenebaumCancerCenter UniversityofMaryland BaltimoreMD21201 USA [email protected] ISBN978-1-60327-266-7 e-ISBN978-1-60327-267-4 DOI10.1007/978-1-60327-267-4 LibraryofCongressControlNumber:2009921125 #HumanaPress,apartofSpringerScienceþBusinessMedia,LLC2009 Allrightsreserved.Thisworkmaynotbetranslatedorcopiedinwholeorinpartwithoutthewritten permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 SpringStreet,NewYork,NY10013,USA),exceptforbriefexcerptsinconnectionwithreviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronicadaptation,computersoftware,orbysimilarordissimilarmethodologynowknownor hereafterdevelopedisforbidden. Theuseinthispublicationoftradenames,trademarks,servicemarks,andsimilarterms,evenifthey arenotidentifiedassuch,isnottobetakenasanexpressionofopinionastowhetherornottheyare subjecttoproprietaryrights. Whiletheadviceandinformationinthisbookarebelievedtobetrueandaccurateatthedateof going to press, neither the authors nor the editors nor the publisher can accept any legal responsibilityforanyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty, expressorimplied,withrespecttothematerialcontainedherein. Printedonacid-freepaper springer.com Preface The chemokine receptors are a diverse family of seven-transmembrane G-protein-coupled receptors binding a large family of ligands. Chemokine receptorswerefirstidentifiedonleukocytesandmediatedirectedmigrationof manyhostcellstositesofligandexpression.Itisnowwellestablishedthatmost malignantcellsalsoexpressoneormorechemokinereceptor.Thisvolumewill summarize the growing body of evidence that several chemokine receptors contributetotumorbehavior. ThereisabundantevidencethatCXCR4,whichiswidelyexpressedinmany malignancies,contributestotheabilityoftumorcellstometastasizetositesof ligandexpression.EvidenceforregulationofCXCR4byhypoxiaisdescribed. LikeCXCR4,bothCCR7andCXCR3functiontopromotetumorcellhoming and metastasis of melanoma, breast and colon cancers. Several chemokine receptors also function to support the survival and proliferation of tumor cells either directly or through transactivation by tyrosine kinase-coupled growthfactorreceptors. While chemokine receptors expressed on tumor cells generally support tumor growth and dissemination, expression of these receptors on host cells has both pro-tumor and anti-tumor functions. Both angiostatic and angiogeneic functions of CXC chemokines acting on endothelial cells have been described. The CXCR3 receptor expressed on malignant cells promotes metastasisbutCXCR3+Th1cellsandNKcellsplayaprotectiveroleinseveral tumor models. Data demonstrating the potential therapeutic potential of CXCR3 ligand overexpression acting on host immune and endothelial cells are also summarized. The CCR5/CCL5 axis has a complex role in tumor behavior with induction of an early protective T-cell response that is ultimatelyoverriddenbyatumorgrowth-promotingroleofCCL5. There are also several chemokine receptors that act as decoy receptors, binding ligands with high affinity. Although these receptors do not transduce signalsthat mediateintracellular responses,ligandbindingdoescontribute to tumorbehavior.Forexample,theD6receptormayactasabiologicalsinkto reducethebioavailabilityofpro-angiogenicchemokines.Differencesindecoy receptor expression in different populations may contribute to disparities in cancerincidenceandoutcome. v vi Preface Thetherapeuticpotentialandchallengesoftargetingchemokinereceptorsin cancer is also discussed. Based on promising preclinical data, antagonists of CXCR4 are currently being evaluated in clinical trials. Initial studies have indicated that inhibition of several other chemokine receptors, expressed on themalignantcell,showspromise;however,thisapproachiscomplicatedbythe factthatmanyprotectivehostcellsexpressthesamereceptors.Insummary,the study of chemokine receptors in cancer has rapidly expanded since the initial description,in2001,ofCXCR4andCCR7incancercells.Manystudiesattest totheimportanceofchemokinereceptorsasdeterminantsoftumorbehavior. The current challenge is to understand the mechanisms underlying these functionsandtomoreeffectivelytargetthesereceptorstherapeutically. AmyM.Fulton Baltimore,MD,USA Contents ChemokinesandChemokineReceptorsinCancerProgression ......... 1 ChareepornAkekawatchai,MarinaKochetkova, JaneHolland,andShaunR.McColl CXCR4andCancer.......................................... 31 BungoFurusatoandJohngS.Rhim HIF-1RegulationofChemokineReceptorExpression ............... 47 ElizabethW.NewcombandDavidZagzag ChemokineReceptorsInvolvedinColonCancerProgression, andLymphNodeMetastasis................................... 63 MakotoMarkTaketoandKenjiKawada TheCXCR3/CXCL3AxisinCancer............................. 79 YanchunLiandAmyM.Fulton RolesforCCR7inCancerBiology .............................. 93 LeiFangandSamT.Hwang TheCCL5/CCR5AxisinCancer ............................... 109 GaliSoriaandAditBen-Baruch CXCChemokinesinCancerAngiogenesis......................... 131 B.MehradandR.M.Strieter TheRolesofChemokinesandChemokineReceptors inProstateCancer........................................... 153 ThorstenEismann,NadineHuber,andAlexB.Lentsch Index..................................................... 171 vii Contributors ChareepornAkekawatchai ChemokineBiologyLaboratory,TheSchoolof MolecularandBiomedicalScience,TheUniversityofAdelaide,Adelaide,SA 5005,Australia AditBen-Baruch DepartmentofCellResearchandImmunology,GeorgeS. WiseFacultyofLifeSciences,TelAvivUniversity,TelAviv69978,Israel ThorstenEismann DepartmentofSurgery,UniversityofCincinnatiCollegeof Medicine,Cincinnati,OH45267-0558,USA LeiFang DermatologyBranch,NationalCancerInstitute,CenterforCancer Research,Bethesda,MD20892,USA AmyM.Fulton MarleneandStewartGreenebaumCancerCenterand Department of Pathology, University of Maryland School of Medicine, 655WestBaltimoreStreet,BaltimoreMD21201,USA BungoFurusato CenterforProstateDiseaseResearch,DepartmentofSurgery, Uniformed Service University of the Health Science, Bethesda, MD 20814; Department of Genitourinary Pathology, Armed Forces Institute of PathologyWashington,DC20307,USA JaneHolland ChemokineBiologyLaboratory,TheSchoolofMolecularand Biomedical Science, North Terrace Campus, Level 5, The University of Adelaide,Adelaide,SA5005,Australia NadineHuber DepartmentofSurgery,UniversityofCincinnatiCollegeof Medicine,Cincinnati,OH45267-0558,USA SamT.Hwang DepartmentofDermatology,MedicalCollegeofWisconsin, Milwaukee,WI53226,USA KenjiKawada DepartmentofSurgery,GraduateSchoolofMedicine,Kyoto University,Sakyo,Kyoto606-8501,Japan ix x Contributors MarinaKochetkova ChemokineBiologyLaboratory,TheSchoolofMolecular and Biomedical Science, The University of Adelaide, Adelaide, SA 5005, Australia AlexB.Lentsch DepartmentofSurgery,UniversityofCincinnatiCollegeof Medicine,Cincinnati,OH45267-0558,USA YanchunLi MarleneandStewartGreenebaumCancerCenter,Universityof MarylandSchoolofMedicine,Baltimore,MD21201,USA ShaunR.McColl ChemokineBiologyLaboratory,TheSchoolofMolecular andBiomedicalScience,TheUniversityofAdelaide,SouthAustralia,5005 BornaMehrad DivisionofPulmonaryandCriticalCareMedicine, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA ElizabethW.Newcomb DepartmentofPathology,NewYorkUniversity Cancer Institute, New York University School of Medicine, New York, NY 10016,USA JohngS.Rhim DepartmentofSurgery,CenterforProstateDiseaseResearch, Uniformed Service University of the Health Science, Bethesda, MD 20814, USA GaliSoria DepartmentCellResearchandImmunology,GeorgeS.Wise FacultyofLifeSciences,TelAvivUniversity,TelAviv69978,Israel RobertM.Strieter DivisionofPulmonaryandCriticalCareMedicine, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA MakotoMarkTaketo DepartmentofPharmacology,GraduateSchool ofMedicine,KyotoUniversity,Sakyo,Kyoto606-8501,Japan DavidZagzag DepartmentofPathologyandDivisionofNeuropathologyand Department of Neurosurgery, New York University Cancer Institute, New YorkUniversitySchoolofMedicine,NewYork,NY10016,USA Chemokines and Chemokine Receptors in Cancer Progression ChareepornAkekawatchai,MarinaKochetkova,JaneHolland, andShaunR.McColl Abstract Directed cell migration is a fundamental component of numerous biologicalsystemsandiscriticaltothepathologyofmanydiseases.Although theimportanceofchemokinesinprovidingnavigationalcuestomigratingcells bearingspecificreceptorsiswell-established,howchemokinefunctionisregu- latedisnotsowellunderstoodandmaybeofkeyimportancetothedesignof newtherapeuticsfornumeroushumandiseases,particularlyforthecontrolof cancergrowthandmetastasis,diseasesinwhichchemokineshaverecentlybeen implicated. In this review, we discuss the general views on the role of specific chemokinesinthesepathologicalprocesses.Inaddition,wediscusstwonovel aspects of chemokine cancer biology; cross-talk between chemokine and growthfactorreceptors,andrefractorychemokinereceptors. Introduction Cancer comprises a large group ofdiseases which share an important charac- teristic of uncontrolled growth. In most tissues and organs, homeostasis is maintainedbyabalancebetweencellproliferationandcelldeath.Occasionally, cellslosetheabilitytorespondtothenormalgrowthcontrolmechanismsand clonesofcellsarisewhichcanexpandtoaconsiderablesizeproducingtumours orneoplasms.Atumourthatremainsinitsoriginallocation,isnotabletogrow indefinitelyanddoesnotinvadesurroundingtissueistermedbenign,whereasa tumourwhichgrowsextensivelyandbecomesinvasiveisknownasamalignant tumourorcancer.Inaddition,mostmalignanttumoursareabletometastasize, aprocessofnewtumourformationandgrowthindistantorgans,whichisthe causeof90%ofhumandeathsfromcancer[115]. Studies on the molecular biology of tumour progression have emphasized the importance of the interaction between the tumour and host homeostatic C.Akekawatchai(*) ChemokineBiologyLaboratory,TheSchoolofMolecularandBiomedicalScience, TheUniversityofAdelaide,Adelaide,SA5005,Australia A.M.Fulton(ed.),ChemokineReceptorsinCancer,CancerDrugDiscovery 1 andDevelopment,DOI10.1007/978-1-60327-267-4_1, (cid:2)HumanaPress,apartofSpringerScienceþBusinessMedia,LLC2009
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