Abstract
Abstract
Developing imaging technology for cancer diagnosis and treatment monitoring is best performed on larger pre-clinical animal models recapitulating tumor growth and metastasis more similar to that found in humans. Such models are amenable to morphological and functional imaging techniques at spatial resolutions appropriate for animal imaging and, translatable to human imaging. In comparison to mouse xenografts, rat models offer the advantages of clinical imaging capabilities, development of xenograft and metastatic models, in orthotopic sites. Human breast cancer cell lines MDA-MB-231 and MCF-7 show a variable take rate in mice, ∼ 68% incurring considerable cost and time. Having a more reproducible method is needed for breast cancer studies. Here we present evidence for development of a novel method in the immune-compromised nude rats. Spheroids grown under stem cell conditions were derived from human breast adenocarcinoma estrogen dependent (MCF-7, ZR-75-1) and independent (MDA-MB-231) lines, and xenografted in both subcutaneous and orthotopic (fat pad) sites in the nude rat. To verify that rat tumors could be studied in detail at spatial resolutions achievable on a clinical 3 Tesla scanner, high-resolution magnetic resonance imaging was performed to identify vascular, viable, and necrotic tumor regions. The breast cancer phenotype and was confirmed by immunohistochemistry for ER and HER2. Tumors were characterized with proliferation marker Ki67, vascularization by CD34 and VEGF, and presence of hypoxic regions by HIF1α. Our results indicated that spheroids from all three lines readily generated tumors independent of exogenous estrogen. MRI is an effective and sensitive method for investigating the biological behavior and vascularization of breast cancer. These findings offer a potential novel method for pre-clinical study and investigation of human breast cancer.
Citation Format: Reza Bayat Mokhtari, Joris Tchouala Nofiele, Syed S. Islam, Herman Yeger, Hai-Ling Margaret Cheng. Investigation of the biological properties of human breast cancer in a nude rat model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1220. doi:10.1158/1538-7445.AM2014-1220