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Spheroid culture of LuCaP 136 patient-derived xenograft enables versatile preclinical models of prostate cancer

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Abstract

LuCaP serially transplantable patient-derived xenografts (PDXs) are valuable preclinical models of locally advanced or metastatic prostate cancer. Using spheroid culture methodology, we recently established cell lines from several LuCaP PDXs. Here, we characterized in depth the features of xenografts derived from LuCaP 136 spheroid cultures and found faithful retention of the phenotype of the original PDX. In vitro culture enabled luciferase transfection into LuCaP 136 spheroids, facilitating in vivo imaging. We showed that LuCaP 136 spheroids formed intratibial, orthotopic, and subcutaneous tumors when re-introduced into mice. Intratibial tumors responded to castration and were highly osteosclerotic. LuCaP 136 is a realistic in vitro–in vivo preclinical model of a subtype of bone metastatic prostate cancer.

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Abbreviations

AR:

Androgen receptor

H&E:

Hematoxylin and eosin

HBS:

HEPES-buffered saline

IHC:

Immunohistochemistry

K5:

Keratin 5

K18:

Keratin 18

MRI:

Magnetic resonance imaging

PCa:

Prostate cancer

PDX:

Patient-derived xenograft

PINP:

N-terminal propeptide of procollagen type 1a

PSA:

Prostate-specific antigen

Te:

Testosterone

μCT:

Micro-computed tomography

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Acknowledgments

This work was supported by the Stanford Department of Urology [HZ, RN, DMP], funding for university level health research in Finland [MPV], a Ferdinand Eisenberger Grant of the German Society of Urology ID SaM1/FE-11 and HOMFOR (Saarland University, Germany) [MS], South-Western Cancer Foundation of Finland and K Albin Johansson Foundation, Finland [JT], Academy of Finland and Sigrid Jusélius Foundation, Finland [PH], The Richard Lucas Foundation and the PNW Prostate Cancer SPORE NIH P50 CA097186 [EC], NIH 2P50CA097186 [IC, PSN, EC], NIH 1R01CA165573 [IC, PSN, EC], NIH P01CA163227 [IC, PSN, EC], and the Prostate Cancer Foundation [EC, DMP]. Pharmatest Services LTD, Turku, Finland, is acknowledged for serum analyses and histological stainings.

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Authors and Affiliations

  1. Department of Urology, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Maija P. Valta, Hongjuan Zhao, Matthias Saar, Rosalie Nolley & Donna M. Peehl

  2. Division of Medicine, Turku University Hospital and University of Turku, Turku, Finland

    Maija P. Valta

  3. Department of Urology and Pediatric Urology, University of Saarland, Homburg/Saar, Germany

    Matthias Saar & Johannes Linxweiler

  4. Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland

    Johanna Tuomela, Jaakko Lehtimäki & Pirkko Härkönen

  5. Cell Imaging Core, Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland

    Jouko Sandholm

  6. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA

    Ilsa Coleman & Peter S. Nelson

  7. Department of Urology, University of Washington, Seattle, WA, 98195, USA

    Peter S. Nelson & Eva Corey

Authors
  1. Maija P. Valta
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  2. Hongjuan Zhao
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  13. Donna M. Peehl
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Correspondence to Donna M. Peehl.

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Valta, M.P., Zhao, H., Saar, M. et al. Spheroid culture of LuCaP 136 patient-derived xenograft enables versatile preclinical models of prostate cancer. Clin Exp Metastasis 33, 325–337 (2016). https://doi.org/10.1007/s10585-016-9781-2

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  • DOI: https://doi.org/10.1007/s10585-016-9781-2

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