MP52-02 CASTRATE RESISTANT GROWTH IN THE BONE NICHE OF NOVEL PATIENT-DERIVED XENOGRAFT MODELS OF BONE METASTATIC PROSTATE CANCER
Christina JamiesonChristina WuAmy StrasnerTakeshi HirataMichelle MuldongJason WooMichael A. LissYoung Beom JeongTomonori YamaguchiSeung Chol ParkHeather LeuSheldon MorrisNicholas A. CacalanoKoichi MasudaCatriona H.M. JamiesonAnna KulidjianChristopher J. Kane
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You have accessJournal of UrologyProstate Cancer: Basic Research V1 Apr 2014MP52-02 CASTRATE RESISTANT GROWTH IN THE BONE NICHE OF NOVEL PATIENT-DERIVED XENOGRAFT MODELS OF BONE METASTATIC PROSTATE CANCER Christina A.M. Jamieson, Christina Wu, Amy Strasner, Takeshi Hirata, Michelle Muldong, Jason R. Woo, Michael A. Liss, Young B. Jeong, Tomonori Yamaguchi, Seung Chol Park, Heather S. Leu, Sheldon R. Morris, Nicholas A. Cacalano, Koichi Masuda, Catriona H.M. Jamieson, Anna A. Kulidjian, and Christopher J. Kane Christina A.M. JamiesonChristina A.M. Jamieson More articles by this author , Christina WuChristina Wu More articles by this author , Amy StrasnerAmy Strasner More articles by this author , Takeshi HirataTakeshi Hirata More articles by this author , Michelle MuldongMichelle Muldong More articles by this author , Jason R. WooJason R. Woo More articles by this author , Michael A. LissMichael A. Liss More articles by this author , Young B. JeongYoung B. Jeong More articles by this author , Tomonori YamaguchiTomonori Yamaguchi More articles by this author , Seung Chol ParkSeung Chol Park More articles by this author , Heather S. LeuHeather S. Leu More articles by this author , Sheldon R. MorrisSheldon R. Morris More articles by this author , Nicholas A. CacalanoNicholas A. Cacalano More articles by this author , Koichi MasudaKoichi Masuda More articles by this author , Catriona H.M. JamiesonCatriona H.M. Jamieson 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.2014.02.1612AboutPDF 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. Bone metastasis leads to debilitating fractures and severe bone pain. It is associated with disease progression, therapy resistance, poor prognosis, and rapid decline. Androgen ablation therapy is standard of care for advanced prostate cancer, however, the role of androgens in bone metastatic prostate cancer is not understood. There are few pre-clinical models to understand the interaction between the bone microenvironment and prostate cancer. Here we report the castrate resistant growth in the bone niche of novel patient-derived intra-femoral xenograft models of prostate bone metastatic cancer. Methods Surgical prostate cancer bone metastasis specimens were transplanted by direct injection into the femurs of Rag2-/-γc-/- mice or sub-cutaneously into the right flank. Patient-derived xenograft (PDX) tumors that grew out were analyzed for prostate cancer biomarker expression using quantitative RT-PCR and immunohistochemistry. Bone lesion formation was measured using micro-computed tomography (μCT). Tumor growth of PCSD1 and PCSD5 were evaluated with calipers and in vivo bioluminescence (IVIS). Results Prostate cancer surgical bone metastasis specimens have been collected from which we have established new serially transplantable, prostate cancer bone metastasis xenograft models – PCSD1, PCSD4 and PCSD5. PCSD1 (Prostate Cancer San Diego 1) and PCSD5 were molecularly characterized as advanced, luminal epithelial-type prostate cancers from different patients. PCSD1 and PCSD5 intra-femoral xenografts formed mixed osteoblastic/osteolytic lesions that closely mimicked those of the patient. PCSD4 metastasized from bone to lymph nodes in mice. Quantitative μCT analysis revealed region-specific bone lesion formation. Treatment with the anti-androgen, bicalutamide, did not inhibit intra-femoral PCSD1 xenograft growth even though there was a decrease in PSA as seen in some patients treated with anti-androgen who had discordant PSA and bone scans. Conclusions PCSD1, PCSD4 and PCSD5 are new patient-derived prostate cancer bone metastasis-derived xenograft models. PCSD1 xenograft model closely recapitulates the mixed osteolytic/osteoblastic bone metastatic lesions seen in patients, and we are using it to develop novel therapies for inhibiting prostate cancer growth in the bone-niche. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e580-e581 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Christina A.M. Jamieson More articles by this author Christina Wu More articles by this author Amy Strasner More articles by this author Takeshi Hirata More articles by this author Michelle Muldong More articles by this author Jason R. Woo More articles by this author Michael A. Liss More articles by this author Young B. Jeong More articles by this author Tomonori Yamaguchi More articles by this author Seung Chol Park More articles by this author Heather S. Leu More articles by this author Sheldon R. Morris More articles by this author Nicholas A. Cacalano More articles by this author Koichi Masuda More articles by this author Catriona H.M. Jamieson 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 ...Cite
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The nationally-recognized Susquehanna
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