Abstract 1400: Mouse models for detection of circulating tumor cells from breast cancer

Abstract

Listen

Translate article

Abstract Breast cancer is the most frequent malignancy among women, causing at least 373,000 deaths per year worldwide, and in United States alone an estimated 208,000 women were diagnosed with breast cancer in 2010. Recent studies indicate that breast cancer is initiated by breast cancer stem cells (BCSCs) that express CD44+/high CD24-/low surface markers. Mammospheres are non-adherent spherical cell clusters grown in selective culture conditions. Our experimental results using mammosphere cultures of different breast cancer cells such as MDA-MB-231 show drastic enrichment of breast cancer stem-like cells with the phenotype of CD44+/high CD24-/low by flow cytometry analysis. We have implanted mammosphere-derived cells into mammary fat pads of nude mice and sampled blood from such tumor-bearing animals to look for the presence of unique breast cancer cells with metastatic potential {circulating tumor cells (CTCs)}, by scoring for Epcam+/cytokeratin+/CD45- tumor cells using the FDA-approved Veridex CellSearch Sysytem. As these metastatic breast cancer cells stably express ZS-Green protein, isolated ZS-Green positive CTCs are being further subjected to breast cancer-specific multiplexed molecular marker analysis. When a mouse with the metastatic breast cancer cell line - 4T1, stained with the CellVue dye is implanted in mammary fat pads, high levels of metastasis are detected with the CellVue marker in different internal organs such as the lungs, liver, heart and lymph nodes. Fluorescence microscopy analysis of blood withdrawn from animals bearing orthotopic 4T1 breast xenograft tumors, could detect ZS-Green positive mouse breast cancer CTCs. These mouse animal models bearing xenograft tumors are facilitating our understanding of CTC detection as well as analysis methods and also in understanding of human breast cancer metastasis. Open questions we are addressing include heterogeneity of CTCs, relationships in stem cell markers and prognostic markers when CTCs are compared with the primary tumors, relationships between tumor burden and tumor aggressiveness with CTC numbers in this mouse model. In addition the model provides an opportunity for testing candidate therapeutic agents and drug combinations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1400. doi:1538-7445.AM2012-1400