Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy

Tumati,Vasu; Mathur,Sanjeev; Song,Kwang; Hsieh,Jer-Tsong; Zhao,Dawen; Takahashi,Masaya; Dobin,Timothy; Gandee,Leah; Solberg,Timothy   D.; Habib,Amyn  A.; Saha,Debabrata

doi:10.3892/ijo.2013.1858

May 2013 Volume 42 Issue 5

Full Size Image

Cover Legend PDF

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

May 2013 Volume 42 Issue 5

Full Size Image

Cover Legend PDF

Article

Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy

Authors:
- Vasu Tumati
- Sanjeev Mathur
- Kwang Song
- Jer-Tsong Hsieh
- Dawen Zhao
- Masaya Takahashi
- Timothy Dobin
- Leah Gandee
- Timothy D. Solberg
- Amyn A. Habib
- Debabrata Saha
View Affiliations / Copyright

Affiliations: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA, Uniformed Services University of Health Sciences (USUHS), Bethesda, MD 20814, USA, Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA, Department of Advanced Imaging, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Pages: 1613-1619
|
Published online on: March 19, 2013

https://doi.org/10.3892/ijo.2013.1858
Expand metrics +

Abstract

The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3‑KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments.

View Figures

View References

1.	Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar
2.	Coen JJ, Zietman AL, Thakral H and Shipley WU: Radical radiation for localized prostate cancer: local persistence of disease results in a late wave of metastases. J Clin Oncol. 20:3199–3205. 2002. View Article : Google Scholar : PubMed/NCBI
3.	Li T, Thongphiew D, Zhu X, et al: Adaptive prostate IGRT combining online re-optimization and re-positioning: a feasibility study. Phys Med Biol. 56:1243–1258. 2011. View Article : Google Scholar : PubMed/NCBI
4.	De Crevoisier R, Tucker SL, Dong L, et al: Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy. Int J Radiat Oncol Biol Phys. 62:965–973. 2005.
5.	Kong Z, Xie D, Boike T, et al: Downregulation of human DAB2IP gene expression in prostate cancer cells results in resistance to ionizing radiation. Cancer Res. 70:2829–2839. 2010. View Article : Google Scholar : PubMed/NCBI
6.	Kong Z, Raghavan P, Xie D, et al: Epothilone B confers radiation dose enhancement in DAB2IP gene knock-down radioresistant prostate cancer cells. Int J Radiat Oncol Biol Phys. 78:1210–1218. 2010. View Article : Google Scholar : PubMed/NCBI
7.	Pidikiti R, Stojadinovic S, Speiser M, et al: Dosimetric characterization of an image-guided stereotactic small animal irradiator. Phys Med Biol. 56:2585–2599. 2011. View Article : Google Scholar : PubMed/NCBI
8.	Saha D, Watkins L, Yin Y, et al: An orthotopic lung tumor model for image-guided microirradiation in rats. Radiat Res. 174:62–71. 2010. View Article : Google Scholar : PubMed/NCBI
9.	Xie D, Gore C, Zhou J, et al: DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell survival and apoptosis. Proc Natl Acad Sci USA. 106:19878–19883. 2009. View Article : Google Scholar : PubMed/NCBI
10.	Xie D, Gore C, Liu J, et al: Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis. Proc Natl Acad Sci USA. 107:2485–2490. 2010. View Article : Google Scholar : PubMed/NCBI
11.	Raheem O, Kulidjian AA, Wu C, et al: A novel patient-derived intra-femoral xenograft model of bone metastatic prostate cancer that recapitulates mixed osteolytic and osteoblastic lesions. J Transl Med. 9:1852011. View Article : Google Scholar
12.	Shikanov S, Shikanov A, Gofrit O, Nyska A, Corn B and Domb AJ: Intratumoral delivery of paclitaxel for treatment of orthotopic prostate cancer. J Pharm Sci. 98:1005–1014. 2009. View Article : Google Scholar : PubMed/NCBI
13.	Tse BW, Russell PJ, Lochner M, Forster I and Power CA: IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms. PLoS One. 6:e242412011. View Article : Google Scholar : PubMed/NCBI
14.	Dunning WF: Prostate cancer in the rat. Natl Cancer Inst Monogr. 12:351–369. 1963.
15.	Lubaroff DM and Culp DA: Experience with an animal model for the study of prostatic carcinoma. Trans Am Assoc Genitourin Surg. 69:72–77. 1977.PubMed/NCBI
16.	Lubaroff DM, Canfield L, Feldbush TL and Bonney WW: R3327 adenocarcinoma of the Copenhagen rat as a model for the study of the immunologic aspects of prostate cancer. J Natl Cancer Inst. 58:1677–1689. 1977.PubMed/NCBI
17.	Lopez DM and Voigt W: Adenocarcinoma R-3327 of the Copenhagen rat as a suitable model for immunological studies of prostate cancer. Cancer Res. 37:2057–2061. 1977.PubMed/NCBI
18.	Vieweg J, Rosenthal FM, Bannerji R, et al: Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines. Cancer Res. 54:1760–1765. 1994.PubMed/NCBI
19.	Rao BR, Slotman BJ, Geldof AA and Perez CA: Radiation sensitivity of Copenhagen rat prostatic carcinoma (R3327-AT and R3327-MATLyLu). Int J Radiat Oncol Biol Phys. 20:981–985. 1991. View Article : Google Scholar : PubMed/NCBI
20.	Vaupel P, Kallinowski F and Okunieff P: Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 49:6449–6465. 1989.PubMed/NCBI
21.	Szentirmai O, Baker CH, Lin N, et al: Noninvasive bioluminescence imaging of luciferase expressing intracranial U87 xenografts: correlation with magnetic resonance imaging determined tumor volume and longitudinal use in assessing tumor growth and antiangiogenic treatment effect. Neurosurgery. 58:365–372. 2006.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Related Articles