Secreted Gaussia Luciferase as a Biomarker for Monitoring Tumor Progression and Treatment Response of Systemic Metastases 英文参考文献.docVIP

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Secreted Gaussia Luciferase as a Biomarker for Monitoring Tumor Progression and Treatment Response of Systemic Metastases 英文参考文献.doc

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Secreted Gaussia Luciferase as a Biomarker for Monitoring Tumor Progression and Treatment Response of Systemic Metastases 英文参考文献

SecretedGaussiaLuciferaseasaBiomarkerfor MonitoringTumorProgressionandTreatmentResponse ofSystemicMetastases EuiheonChung1.,HiroshiYamashita1.,PatrickAu1,BakhosA.Tannous2,3*,DaiFukumura1*, RakeshK.Jain1* 1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America,2MolecularNeurogeneticsUnit,DepartmentofNeurology,MassachusettsGeneralHospital,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesof America,3Department ofRadiology, Center forMolecularImaging Research, MassachusettsGeneral Hospital, HarvardMedicalSchool, Boston, Massachusetts, United StatesofAmerica Abstract Background: Currently, only few techniques are available for quantifying systemic metastases in preclinical model. Thus techniques that can sensitively detect metastatic colonization and assess treatment response in real-time are urgently needed.Tothisend,weengineeredtumorcellstoexpressanaturallysecretedGaussialuciferase(Gluc),andinvestigatedits useasacirculatingbiomarkerformonitoringviablemetastaticorprimarytumorgrowthandtheirtreatmentresponses. Methodology/PrincipalFindings:Wefirstdevelopedorthotopicprimaryandmetastaticbreasttumorswithderivativeof MDA-MB-231cellsexpressingGluc.WethencorrelatedtumorburdenwithGlucactivityinthebloodandurinealongwith bioluminescent imaging (BLI). Second, we utilized blood Gluc assay to monitor treatment response to lapatinib in an experimentalmodelofsystemicmetastasis.WeobservedgoodcorrelationbetweentheprimarytumorvolumeandGluc concentration inblood(R2=0.84)andurine(R2=0.55) inthebreast tumormodel.Thecorrelation deviatedas aprimary tumorgrewduetoareductioninviabletumorfraction.Thiswasalsosupportedbyourmathematicalmodelsfortumor growth to compare the total and viable tumor burden in our model. In the experimental metastasis model, we found numerous brain metastases as well as systemic metastases including bone and lungs. Importantly, blood Gluc assay reve