MP62-12 ORTHOTOPIC XENOGRAFTS USING LUCAP136 SPHEROID CULTURES PROVIDE A VERSATILE PRECLINICAL MODEL OF PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I1 Apr 2016MP62-12 ORTHOTOPIC XENOGRAFTS USING LUCAP136 SPHEROID CULTURES PROVIDE A VERSATILE PRECLINICAL MODEL OF PROSTATE CANCER Matthias Saar, Johannes Linxweiler, Maija Valta, Christina Körbel, Andreas Müller, Kerstin Junker, Michael Stöckle, Michael D. Menger, and Donna M Peehl Matthias SaarMatthias Saar More articles by this author , Johannes LinxweilerJohannes Linxweiler More articles by this author , Maija ValtaMaija Valta More articles by this author , Christina KörbelChristina Körbel More articles by this author , Andreas MüllerAndreas Müller More articles by this author , Kerstin JunkerKerstin Junker More articles by this author , Michael StöckleMichael Stöckle More articles by this author , Michael D. MengerMichael D. Menger More articles by this author , and Donna M PeehlDonna M Peehl More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.920AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PCa) research is still hampered by a limited number of well characterized models that adequately display intraprostatic tumor growth and progression. In this study we aimed to develop an authentic preclinical model of prostate cancer by combining an orthotopic xenografts with LuCaP136 spheroids - a recently developed 3D cell culture, that has some valuable properties like PTEN loss, TP53 mutation, wild-type AR and an osteosclerotic phenotype in intratibial xenograft models. METHODS 5x105 LuCaP136 spheroid cells were injected into the prostate of 6 CB17-SCID mice. Orthotopic tumor growth was monitored by 3D-ultrasonography (3D-US), contrast-enhanced in-vivo micro-CT (CE-CT) as well as 9.4T MRI. Furthermore, serum-PSA was measured 5 and 7 weeks after orthotopic implantation. After the sacrifice tumors were analyzed by conventional histology (H&E) as well as immunohistochemistry (IHC; PSA, AMACR, AR, ERG, Ki67). RESULTS Fast growing (doubling time = 12.4 days) orthotopic tumors developed in all mice and could be detected by 3D-US (Fig. 1A) and T2-weighted MRI (Fig. 1B) as early as 3 weeks after injection. Additionally acquired MRI sequences demonstrated restricted diffusion as it is typical for highly cellular tumors (DWI/ADC map; Fig. 1C) as well as intratumoral hemorrhage (T2*; Fig. 1D). CE-CT could not visualize the tumors properly. The mice had low but detectable PSA serum-levels with the mean almost doubling from the first (w5; 0.16ng/ml) to the second (w7; 0.29ng/ml) control. Tumor volumes determined by 3D-US and MRI showed a strong correlation among each other (r=0.963) as well as simultaneously measured PSA-levels (r=0.848 and r=0.844). At autopsy orthotopic tumors proved to be solid, highly vascularized (Fig. 1E) with signs of invasive growth. IHC showed positive AR, PSA and AMACR signals, ERG was negative. Ki67 proliferation index was close to 100% (Fig. 1F). CONCLUSIONS Orthotopic xenografts from LuCaP136 spheroids provide a realistic preclinical in-vivo model of PCa with multimodal imaging and serum-PSA serving as innovative tools to monitor tumor growth over time. Whether this model leads to the spontaneous development of especially osseous metastases is subject of current investigations. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e816-e817 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Matthias Saar More articles by this author Johannes Linxweiler More articles by this author Maija Valta More articles by this author Christina Körbel More articles by this author Andreas Müller More articles by this author Kerstin Junker More articles by this author Michael Stöckle More articles by this author Michael D. Menger More articles by this author Donna M Peehl More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...