Abstract P1-07-24: Modeling breast cancer metastasis in the mouse via measurement of circulating tumor cells
Authors: Jennifer L Gorman, Michael Parsons, Eldad Zacksenhaus, Sean Egan, Martin Chang, Jim R Woodgett
Journal: Cancer Research (2015)

Abstract Objectives: Advances in the detection of circulating tumor cells (CTC) in the blood of metastatic breast cancer patients have indicated that patients with greater than 5 CTC/7.5mL of blood have poorer prognosis; however, little is known about the biology of these cells and what characteristics are critical for breast tumor cell dissemination. We are developing and evaluating several mouse models of breast cancer to characterize important markers that distinguish CTCs from other cell types in the blood as well as to assess whether silencing of various metastasis supporting genes leads to reductions in CTC counts and formation of metastatic tumors. Methods: This study involves two separate approaches to characterize CTCs. The first involves xenograft models using human breast cancer cells injected into the fat pad of immunocompromised mice. These cells are tagged with both mCherry, for detection in blood, and luciferase, to track metastatic spread of the primary tumor cells to other sites via intravital imaging. Blood was collected from tumor bearing mice at end point, processed and stained for characterized CTC markers. The second approach involves endogenous mouse models to characterize CTC counts and relevant markers in a variety of metastatic and non-metastatic murine breast cancer models using negative depletion to remove contaminating normal and hematopoietic cells. In both approaches CTCs have been assessed using the Imagestream by Amnis. Results: Initial xenograft experiments with MDA-MB-231 cells injected into the mouse mammary gland fat pad revealed a low concentration of mCherry+/cytokeratin+/Hoechst+/CD45- cells in the blood of mice without confirmed metastatic dissemination. Pilot studies on endogenous tumor models have demonstrated the utility of our negative depletion approach to remove contaminating hematopoietic cells as well as the detection of a population of EpCAM+/Hoechst+/CD45- cells. Conclusions: Initial experiments have provided feasibility for detailed characterization of mouse CTCs, which will be presented. This work complements our study being carried out on characterizing CTCs in metastatic breast cancer patients. Increasing understanding of the biology of circulating tumor cells and relating their characteristics to those of both the primary and metastatic tumors may reveal mediators common and functionally important to all 3 tumor cell populations and may therefore serve as better targets for treatments that are effective against both the primary and metastatic tumors. Citation Format: Jennifer L Gorman, Michael Parsons, Eldad Zacksenhaus, Sean Egan, Martin Chang, Jim R Woodgett. Modeling breast cancer metastasis in the mouse via measurement of circulating tumor cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-24.