pthrp_2c1-34_对小鼠乳腺癌骨转移的影响

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1、PTHrPl-34对小鼠乳腺癌骨转移的影响THEEFFECToFPTHrPl．34ONBON。EMETASTASISOFMoUSEBREASTCANCERCELLSPostgraduateTutorProfessorSpecialtyLiYupuJiHongMedicine(Endocrineandmetabolicdisease)ABSTRACTObjectiveBonemetastasesCanOCCUrinmanytypesofcancer,suchasbreastcarcinoma,lungcanseTandrenalcellcarcinoma．Theinteractio

2、noftumorcells，bone-formingosteoblasts，bone—resorbingosteoclastsandthebonematrixstimulatetheestablishmentanddevelopmentofcancerosteolyticbonemetastases．Tumorcellssecretefactorsthatstimulatebonemetastasesandmakebonedestruction，Thebonematrixcontainsavaststorehouseofgrowthfactorswhichalesynthesiz

3、edbyosteoblastsandreleasedbyosteoclasticboneresorption,attainhi．ghconcentrationswithinthebonemicroenvironmentandcallattracttunlorcellstoboneandpromotemetastaticgrowth．ManyofthefactorsinvolvedinthisviciouscyclesuchasPTHrP,TGF—B，RANKLremainareasofactiveinvestigation．Parathyroidhormone-relatedpr

4、otein(PTHrP)issecretedbyavarietyofceilsandholdsextensivebiologicalfunctions．SomestudiesshowthatPTHrPisoverexpressedbyavarietyoftumors，itisoneofthemainmediatedfactorofosteoclastactivity,inducingosteoclastdifferentiationandmaturation,playinganimportantroleintheestablishmentanddevelopmentofbreas

5、tcancerosteolyticbonemetastases．Takebreastcansetasanexample，MoststudiesshowthatPTHrPisamajorcandidatefactorresponsiblefortheosteoclasticboneresorptionpresentatsitesofbreastcarcinomametastatictobone．However,somestudiesshowthatPTHrP—positivetumorswereindependentlypredictiveofimprovedpatientsurv

6、ival，PTHrPproductionbybreastcancercellsconfersonthemalessmalignantphenotype，onethatislessinvasiveandlesslikelytoresultinmetastasisformationatallsites，includingbone．Inthisexperimentwe-5-山东省医学科学院硕士学位论文establishmousebreastcancermodeltoinvestigatetheeffectofpersistenthJ}gh-dosePTHrPonbreastcancer

7、bonemetastasisandbonemetabolismbyX—ray,pathologicalsectionandtestingbiochemicalmarkersofboneturnover，biomechanicalresponse，aswellastoobservetumorgrowth．Layafoundationforthedevelopmentofanti-PTHrPantibodytoinhibittumorbonemetastasis．MethodsInp