Abstract 42: Triple negative breast cancer cell heterogeneity in zebrafish-host microenvironment

Abstract

Abstract Metastatic triple negative breast cancer (TNBC) can be considered as incurable endpoint in the progression of TNBC, prevention or treatment of metastasis therefore is of paramount importance. New insights into intra-tumoral heterogeneity have cast light on the existence of multiple functionally distinct cellular entities within one tumor, among others these cells can be divided based on their metastatic potential. The zebrafish provides us with the unique opportunity to study the first steps of metastatic initiation in great detail both microscopically and transcriptionally, on the side of both the host and cancer cells. Organotropic TNBC lines engrafted into this model recapitulate the tropism found in higher vertebrates. Using our zebrafish TNBC xenograft model we study these cellular sub-populations in vivo during metastatic initiation. These small metastatic lesions can be further analyzed ex vivo through the re-isolation of novel zebrafish specific organotropic cell lines. Re-engraftment of these greatly enhances the tumorigenic potential, and transcriptional analysis reveals increased EMT plasticity and an induction of stemness markers. Engraftment of these cells into murine tibia shows a significantly increased tumorigenic and osteolytic potential, further underscoring the critical role of this sub-population in cancer initiation. To determine the genetic drivers of this process we performed whole exome sequenced (NGS) of both, in vitro cultured cancer cells (maternal and re-isolated) and micro-dissected tissue samples derived from in situ zebrafish xenograft material. We are currently in the process of evaluating the candidate genes underpinning the enhanced tumorigenic potential in both the zebrafish and murine models used. Citation Format: B.Ewa Snaar-Jagalska, Arwin Groenewoud, Letizia Astrologo, Lanpeng Chen, Marianna Kruithof-de Julio. Triple negative breast cancer cell heterogeneity in zebrafish-host microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 42.