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Metastasizing, Luciferase Transduced MAT‑Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug
Tumour Biology Center, Clinical Research, Department Lipids & Liposomes, Breisacher Str.117, D-79106 Freiburg, Germany
ProQinase GmbH, Breisacher Str.117, D-79106 Freiburg, Germany
Laboratory for Design of Microsystems, Department of Microsystems Engineering (IMTEK), Georges-Köhler-Allee 106, D-79110 Freiburg, Germany
Present address: Roche Diabetes Care AG, Kirchbergstrasse 190. CH-3401 Burgdorf, Switzerland
* Author to whom correspondence should be addressed.
Received: 4 May 2011; in revised form: 16 May 2011 / Accepted: 16 June 2011 / Published: 17 June 2011
Abstract: The most fatal outcomes of prostate carcinoma (PCa) result from hormone-refractory variants of the tumor, especially from metastatic spread rather than from primary tumor burden. The goal of the study was to establish and apply rat MAT-Lu prostate cancer tumor models for improved non-invasive live follow up of tumor growth and metastasis by in vivo bioluminescence. We established luciferase transduced MAT-Lu rat PCa cells and studied tumor growth and metastatic processes in an ectopic as well as orthotopic setting. An intravenous bolus treatment with doxorubicin was used to demonstrate the basic applicability of in vivo imaging to follow up therapeutic intervention in these models. In vitro analysis of tissue homogenates confirmed major metastatic spread of subcutaneous tumors into the lung. Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively). Preliminary data of orthotopic implantation (three animals) showed metastatic invasion to investigated organs in all animals but with varying preference (e.g., to lymph nodes). Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis. Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.
Keywords: prostate cancer; MAT-Lu; orthotopic; bioluminescence; luciferase; rat; dunning
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Jantscheff, P.; Esser, N.; Geipel, A.; Woias, P.; Ziroli, V.; Goldschmidtboing, F.; Massing, U. Metastasizing, Luciferase Transduced MAT‑Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug. Cancers 2011, 3, 2679-2695.
Jantscheff P, Esser N, Geipel A, Woias P, Ziroli V, Goldschmidtboing F, Massing U. Metastasizing, Luciferase Transduced MAT‑Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug. Cancers. 2011; 3(2):2679-2695.
Jantscheff, Peter; Esser, Norbert; Geipel, Andreas; Woias, Peter; Ziroli, Vittorio; Goldschmidtboing, Frank; Massing, Ulrich. 2011. "Metastasizing, Luciferase Transduced MAT‑Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug." Cancers 3, no. 2: 2679-2695.