Experimental orthotopic prostate tumor in nude mice: Techniques for local cell inoculation and three-dimensional ultrasound monitoring☆

Saar, Matthias; Körbel, Christina; Jung, Volker; Suttmann, Henrik; Grobholz, Rainer; Stöckle, Michael; Unteregger, Gerhard; Menger, Michael D.; Kamradt, Jörn

doi:10.1016/j.urolonc.2010.02.014

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Experimental orthotopic prostate tumor in nude mice: Techniques for local cell inoculation and three-dimensional ultrasound monitoring☆☆

Matthias Saar, M.D.
- Clinic of Urology and Pediatric Urology, University of Saarland, Homburg/Saar, Germany
- Corresponding author. Tel.: +49-6841-1624788; fax: +49-6841-1624795.
Christina Körbel, D.V.M.
- Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
Volker Jung, Ph.D.
- Clinic of Urology and Pediatric Urology, University of Saarland, Homburg/Saar, Germany
Henrik Suttmann, M.D.
- Urologikum Hamburg, Hamburg, Germany
Rainer Grobholz, M.D.
- Institute of Pathology, University of Saarland, Homburg/Saar, Germany
Michael Stöckle, M.D.
- Clinic of Urology and Pediatric Urology, University of Saarland, Homburg/Saar, Germany
Gerhard Unteregger, Ph.D.
- Clinic of Urology and Pediatric Urology, University of Saarland, Homburg/Saar, Germany
Michael D. Menger, M.D.
- Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
Jörn Kamradt, M.D.
- Clinic of Urology and Pediatric Urology, University of Saarland, Homburg/Saar, Germany

Received 15 December 2009; received in revised form 23 February 2010; accepted 25 February 2010. published online 10 May 2010.
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Abstract

Objectives

Orthotopic prostate cancer models are of great importance for cancer research. Orthotopic models in mice have been described previously. However, these studies lack a detailed methodological description and fail to define standards for local cell inoculation. Herein, we studied the effect of different protocols on tumor growth and report for the first time the use of high resolution ultrasound for monitoring of tumor growth.

Materials and methods

Orthotopic inoculation of DU 145 MN1 prostate cancer cells was performed in 30 nude mice varying (1) the amount of cells (5 × 10⁵ vs. 5 × 10⁴), (2) the number of puncture sites, and (3) the addition of matrigel. Surgical complications such as recoil of cells through the injection canal and rupture of the prostatic capsule were monitored. Animals were tracked by ultrasound imaging after 4, 5, and 6 weeks. Autopsy and histology confirmed local tumor growth.

Results

A take rate of 27/30 (90%) was observed. Growth of orthotopic prostate tumors was increased after inoculation of a large amount of cells under the capsule of 1 dorsal prostate lobe, but inoculation of small amounts of cells still induced local tumors. Noninvasive ultrasound examination allowed to identify orthotopic tumor formation and to monitor tumor growth in vivo. Addition of matrigel did not accelerate tumor growth. Complications like recoil (6.8%) or rupture of the prostate capsule (1.4%) were rare.

Conclusions

Inoculation of DU 145 MN1 cells under the prostate capsule with a defined procedure results in very high take rates. Ultrasound screening is feasible to repetitively monitor tumor growth.

Keywords: Prostate cancer, Orthotopic tumor growth, Xenograft model, Ultrasound