Abstract 4726: Gene expression signatures of isolated circulating tumor cells from metastatic breast cancer patients reveal presence of breast cancer stem cells with EMT or MET phenotypes

Abstract

Abstract Breast cancer stem cells are responsible for tumor recurrence, metastasis and drug resistance. One of the important steps in metastasis is entry of tumor cells into the blood circulation. These circulating tumor cells (CTCs) may serve as markers of cancer progression and as a “liquid biopsy” to provide information on tumor biology at single cell resolution. Current methods of CTC capture are not fully inclusive to isolate all phenotypic variations of cancer stem cells (CSCs) among the CTCs. Using newly developed microfluidic methods to isolate CTCs from blood samples of metastatic breast cancer patients, we assessed gene expression profiles in these cells. The gene expression signatures of isolated CTCs were determined using a highly sensitive microfluidic-based 96-plex RT-qPCR method. Analyzed multiplex RT-qPCR data revealed distinct gene expression patterns among CTCs isolated from different patients. Cancer stem cell markers such as ALDH1a1, ALDH1a2 and ALDH1a3 as well as CD44 and CD24 genes were differentially expressed in isolated CTCs. In addition, markers of the epithelial to mesenchymal (EMT) and mesenchymal to epithelial (MET) phenotypes such as Vimentin, EpCAM, HER2, CDH1, CDH2, TGFb1 and cytokeratins were also expressed variably in the CTC samples. Furthermore, MMP9, TIMP1, CD90, CD14, SPARC, BRAF, KRAS, PI3K and ERCC1 genes which play a role in cancer initiation, promotion, metastasis and drug resistance were also differentially expressed in the isolated CTCs. Overall, these studies further our understanding into the heterogeneity of CTCs and CSCs as well as providing a potential tool for real-time monitoring of cancer patients on clinical trials. Citation Format: Shamileh Fouladdel, Hyeun Joong Yoon, Eric Lin, Tae Hyun Kim, Yadwinder S. Deol, Tahra K. Luther, Shawn G. Clouthier, Hui Jiang, Monika L. Burness, Sunitha Nagrath, Ebrahim Azizi, Max S. Wicha. Gene expression signatures of isolated circulating tumor cells from metastatic breast cancer patients reveal presence of breast cancer stem cells with EMT or MET phenotypes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4726. doi:10.1158/1538-7445.AM2015-4726