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.
Highlights
Mortality in prostate carcinoma (PCa) is mostly due to the hormone-refractory metastasizing variant of the tumor
Androgen independent Dunning rat prostate cancer cells, AT-1, AT-3.1, MAT-Lu or MAT LyLu consistently show a clearly augmented resistance to various cytotoxic drugs resulting from increased activity of the rat mdr1b gene, the homologue to the human MDR1 gene [10]
The growth of subcutaneous implanted MAT-Lu ELN PCa was followed up every other day by callipering (Figure 1A)
Summary
Mortality in prostate carcinoma (PCa) is mostly due to the hormone-refractory metastasizing variant of the tumor. Androgen independent Dunning rat prostate cancer cells, AT-1, AT-3.1, MAT-Lu or MAT LyLu consistently show a clearly augmented resistance to various cytotoxic drugs resulting from increased activity of the rat mdr1b gene, the homologue to the human MDR1 gene [10]. They display distinct and strong metastatic capacities [11] and behave similar to advanced human prostate cancer cells, and are valuable models for experimental in vivo studies in rats
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
