A1 Refereed original research article in a scientific journal
Tissue slice grafts of human renal cell carcinoma: An authentic preclinical model with high engraftment rate and metastatic potential – An authentic preclinical model with high engraftment rate and metastatic potential
Subtitle: An authentic preclinical model with high engraftment rate and metastatic potential
Authors: Alan E. Thong, Hongjuan Zhao, Alexandre Ingels, Maija P. Valta, Rosalie Nolley, Jennifer Santos, Sarah R. Young, Donna M. Peehl
Publication year: 2014
Journal: Urologic Oncology: Seminars and Original Investigations
Volume: 32
Issue: 1
First page : 43.e23
Last page: 43.e30
Number of pages: 8
ISSN: 1078-1439
eISSN: 1873-2496
DOI: https://doi.org/10.1016/j.urolonc.2013.05.008
Objective: Discovery ofcurativetherapiesforrenalcellcarcinoma(RCC)ishamperedbylackofauthenticpreclinicalmodels.
Tumorgrafts, generatedbydirectimplantationofpatient-derivedtissuesintomice,havedemonstratedsuperiorabilitytopredicttherapeutic
response. Weevaluated “tissue slicegrafts” (TSGs) asanimprovedtumorgraftmodelofRCC.
Materials andmethods: Cores offreshRCCwereprecision-cutat300 mm andimplantedundertherenalcapsuleofRAG2−/−γC−/−
mice. Engraftmentrate,histology,biomarkerexpression,genetic fidelity, andmetastaticpotentialwereevaluated.Magneticresonance
imaging (MRI)wastestedasanoninvasivemethodtomeasuretumorvolume,andresponsetoatargetedtherapywasdetermined.
Results: All 13casesofRCCengraftedanddisplayedcharacteristichistologyandbiomarkers.TSGvolumequantified noninvasivelyby
MRI highlycorrelatedwithgraftweights,providingauniquetoolformonitoringorthotopicgrowth.Moreover,in2cases,cancercellsfrom
TSGs metastasizedtoclinicallyrelevantsites,includingbone.MicroarrayanalysisandDNAsequencingdemonstratedahighdegreeof
correlation ofglobalgeneexpressionandvonHippel-Lindau(VHL)statusbetweenTSGsandparentaltumors.TreatmentofTSGswith
sunitinib significantly decreasedgraftweightandmeanvesseldensitycomparedwithcontrols.
Conclusion: The TSGmodelofRCCfaithfullyrecapitulatestumorpathology,geneexpression,geneticmutation,anddrugresponse.The
high engraftmentrateandmetastaticpotentialofthisauthenticmodel,inconjunctionwiththeabilitytogeneratelarge first-generation animal cohorts andtoquantitatetumorvolumeattheorthotopicsitebyMRI,proffersignificant advantagescomparedwithotherpreclinical platforms.
