Abstract 4686: Stem-like cells and bulk cells in breast cell lines express distinct combinations of Eph receptors and ephrin ligands

Abstract

Abstract Purpose: The maintenance of the breast cancer stem cell niche in mammary tumors has been attributed to aberrant expression of Eph receptors and ephrin ligands. The current study aims to identify Eph receptors and ephrin ligands that may contribute to the tumorigenic and invasive breast cancer phenotypes, and can potentially be used to classify tumor specific stem cells and target them for therapeutic intervention. Methods: The bulk cells and stem-like cells from MCF10A, MCF7 and MDA-MB-231 cell lines were separated based on CD44+/CD24+ and CD44+/CD24- combinations of cell surface markers, respectively. These cell lines represent non-tumorigenic breast epithelium (MCF10A), non-invasive breast carcinoma (MCF7), and invasive triple negative breast carcinoma (MDA-MB-231). The profiles of Eph receptors and ephrin ligands were determined by qPCR. The changes in selected transcripts were confirmed by immunocytochemistry and western blot analysis. Results: Our study revealed that Eph receptors and ephrin ligands have distinct expression signatures in CD44+/CD24- tumor-initiating cells relative to the bulk tumor cell population. Such combinatorial expression of these molecules in stem cells and bulk cells may modulate and maintain breast tumor phenotypes. The differential patterns of expression are evidenced by changes in qualitative as well as quantitative combinations of Eph receptors and ephrin ligands. The levels of EphA8 transcript were notably lower in CD44+/CD24- cells as compared to bulk MCF7 cells. However, EphA8 was significantly upregulated in stem cells as compared to bulk cells isolated from MDA-MB-231 cell line. Conclusion: The relative abundance of Eph receptors and ephrin ligands in stem and bulk cells provides molecular signatures of stem cells specific to tumor phenotypes. The combinatorial expression of these molecules corresponds to invasiveness of breast cancer cells, which can be potentially exploited for diagnostics and therapeutics. Citation Format: Mariana Lucero, Jaspreet Thind, Shayan Senaati, Belinda Jimenez, Tanin Zadeh, Raj P. Kandpal. Stem-like cells and bulk cells in breast cell lines express distinct combinations of Eph receptors and ephrin ligands [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 4686.