Mp61-14 microct analysis revealed bone region-specific localization of osteolytic versus osteoblastic lesions in pcsd1, a new patient-derived xenograft model of bone metastatic prostate cancer.

You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2015MP61-14 MICROCT ANALYSIS REVEALED BONE REGION-SPECIFIC LOCALIZATION OF OSTEOLYTIC VERSUS OSTEOBLASTIC LESIONS IN PCSD1, A NEW PATIENT-DERIVED XENOGRAFT MODEL OF BONE METASTATIC PROSTATE CANCER. Christina Jamieson, Takeshi Hirata, Seung Chol Park, Christina N. Wu, Michelle Muldong, Elana Godebu, Amy Strasner, Jason R. Woo, Omer Raheem, Tomonori Yamaguchi, Hiromi Kumon, Nicholas A. Cacalano, Catriona H.M. Jamieson, Koichi Masuda, Anna A. Kulidjian, and Christopher J. Kane Christina JamiesonChristina Jamieson More articles by this author , Takeshi HirataTakeshi Hirata More articles by this author , Seung Chol ParkSeung Chol Park More articles by this author , Christina N. WuChristina N. Wu More articles by this author , Michelle MuldongMichelle Muldong More articles by this author , Elana GodebuElana Godebu More articles by this author , Amy StrasnerAmy Strasner More articles by this author , Jason R. WooJason R. Woo More articles by this author , Omer RaheemOmer Raheem More articles by this author , Tomonori YamaguchiTomonori Yamaguchi More articles by this author , Hiromi KumonHiromi Kumon More articles by this author , Nicholas A. CacalanoNicholas A. Cacalano More articles by this author , Catriona H.M. JamiesonCatriona H.M. Jamieson More articles by this author , Koichi MasudaKoichi Masuda More articles by this author , Anna A. KulidjianAnna A. Kulidjian More articles by this author , and Christopher J. KaneChristopher J. Kane More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2195AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer bone metastasis occurs in 50-90% of men with advanced disease for which there is no cure. There are few pre-clinical models to understand the interaction between the bone microenvironment and prostate cancer. We established PCSD1, a new patient-derived bone metastasis prostate cancer xenograft model in mice. PCSD1 xenograft tumors were preferentially resistant in the bone-niche to the anti-androgen, bicalutamide. PCSD1 tumor growth resulted in mixed osteolytic and osteoblastic bone lesions, which closely resembled the lesions in the patient. In this study microCT analysis was used to evaluate microstructural changes in this patient-derived xenograft model of bone metastatic prostate cancer. METHODS PCSD1 cells or the Control sample were injected into the right femurs of Rag2-/-γc-/- male mice. MicroCT scanning was performed on mouse femurs 8-10 weeks later. Femurs with injection holes evident in the condyle microCT scans were selected for microstructural analysis (PCSD1 group, n=13, Control group, n=8). RESULTS Both the PCSD1 and Control groups had significantly shortened injected right femurs compared to the un-injected left femurs, however, there were additional significant changes in the femurs of the PCSD1 group. The ratio of bone volume (BV) to total volume (BV/TV) and the total bone volume (BV) were both decreased at the proximal and distal ends of the femurs in the PCSD1 group (p<0.01 respectively). Conversely, in the cortical bone in the middle of bone shaft, BV was increased in the PCSD1 group (p<0.05) and the bone shaft diameter was increased in PCSD1 compared to Control (p<0.01). An abnormal bone extension to the lateral side of the third trochanter of the PCSD1 group was also seen. Differences in the trabecular bone region in the PCSD1 group were either osteolytic or osteoblastic. Histochemical analysis showed PCSD1 cells localized in the affected bone regions. CONCLUSIONS PCSD1-induced bone lesions were osteolytic at the distal and proximal ends of the femur and osteoblastic in the central, cortical bone. Changes in trabecular bone region were either osteoblastic or osteolytic which may be a transitional zone. Thus, microCT analysis revealed bone region-specific changes due to PCSD1 xenograft tumor cell growth in the femur. This pre-clinical model is being used to test the hypothesis that specific bone regions may preferentially support therapy resistance. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e751 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christina Jamieson More articles by this author Takeshi Hirata More articles by this author Seung Chol Park More articles by this author Christina N. Wu More articles by this author Michelle Muldong More articles by this author Elana Godebu More articles by this author Amy Strasner More articles by this author Jason R. Woo More articles by this author Omer Raheem More articles by this author Tomonori Yamaguchi More articles by this author Hiromi Kumon More articles by this author Nicholas A. Cacalano More articles by this author Catriona H.M. Jamieson More articles by this author Koichi Masuda More articles by this author Anna A. Kulidjian More articles by this author Christopher J. Kane More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...