Abstract 4721: Epithelial to mesenchymal transition is not required for breast to lung metastasis but contributes to chemoresistance

Abstract

Abstract The role of epithelial to mesenchymal transition (EMT) in metastasis is a longstanding source of controversy, largely due to an inability to monitor transient and reversible EMT phenotypes in vivo. We have established a novel and unique EMT lineage tracing system in spontaneous breast to lung metastasis models. In these models, mesenchymal-specific Cre-mediated recombination initiates permanent switch of fluorescent markers in tumor cells undergoing EMT. This allows us to track EMT tumor cells in the primary tumor, circulation and distant organs following the trail of breast to lung metastasis in vivo. We confirmed that within a predominantly epithelial primary tumor, a small portion of tumor cells undergo EMT. Strikingly, lung metastases were mainly comprised of non-EMT tumor cells maintaining their epithelial phenotype. Inhibiting EMT by overexpressing miR-200 did not impact lung metastasis development. However, EMT cells significantly contribute to recurrent lung metastasis formation after chemotherapy. These cells survived cyclophosphamide treatment due to reduced proliferation, apoptotic tolerance, and elevated expression of chemoresistance-related genes. This study suggests the potential of an EMT-targeting strategy, in conjunction with conventional chemotherapies, in the treatment of breast cancer patients. Citation Format: Kari R. Fischer, Anna Durrans, Sharrell Lee, Jianting Sheng, Hyejin Choi, Fuhai Li, Stephen Wong, Nasser K. Altorki, Vivek Mittal, Dingcheng Gao. Epithelial to mesenchymal transition is not required for breast to lung metastasis but contributes to chemoresistance. [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 4721. doi:10.1158/1538-7445.AM2015-4721