Abstract 972: Direct observation in living tumors shows macrophage-dependent induction and dissemination of cancer stem cells in breast cancer

Cancer stem cells (CSCs) play an important role during metastatic progression of breast cancer. However, the in vivo properties and dynamic behavior of CSCs are not well understood. Here, we employed high-resolution intravital multiphoton microscopy using a SOX2/OCT4 responsive fluorescent stem cell biosensor to directly observe CSC dynamics in the living animal using an orthotopic breast cancer xenograft model. We report that CSCs constitute a minority population (1-3%) in the primary tumors, and display the slow-migratory, invasive phenotype that is specifically associated with disseminating tumor cell population. We also report, for the first time, that CSCs are preferentially localized in direct contact with macrophages near and in tumor microenvironment of metastasis (TMEM) sites, the macrophage-containing intravasation doorway for tumor cells and that CSCs metastasize to lung and are strikingly enriched in early lung metastatic colonies. This is explained by our observation that, in vitro and in vivo, direct physical contact with macrophages induces stemness in non-stem cancer cells via juxtacrine Notch-Jagged1 signaling. These data indicate for the first time that macrophages play an actively inductive role in the CSC niche and promote TMEM-mediated CSC intravasation and early metastatic seeding. Citation Format: Ved P. Sharma, Yarong Wang, Binwu Tang, George S. Karagiannis, Emily A. Xue, David Entenberg, Lucia Borriello, Anouchka Coste, Chinmay R. Surve, Dominic Esposito, Maja H. Oktay, Lalage M. Wakefield, John S. Condeelis. Direct observation in living tumors shows macrophage-dependent induction and dissemination of cancer stem cells in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 972.