Abstract PO-030: Characterizing mechanisms for inhibiting metastasis in triple negative breast cancer

Abstract

Abstract Tumor cell heterogeneity has been strongly implicated in metastatic progression of solid tumors such as breast cancer, leading to resistance and recurrence. We hypothesize that inhibiting metastasis will reduce tumor cell heterogeneity and thereby increase therapeutic sensitivity. To test this hypothesis, we expressed the metastasis suppressor Raf Kinase Inhibitory Protein (RKIP or PEBP1) in triple-negative breast cancer (TNBC) cells as a means of comparing the variation in gene expression between individual cells in metastatic versus non-metastatic tumors. Xenograft tumors with or without exogenous RKIP expression were dissociated into single cell suspensions. We removed mouse as well as dead cells, and the remaining cells were loaded onto a Fluidigm C1 high-throughput chip for separation and library preparation. For each condition we performed three independent experiments yielding a total of 1569 cells. We performed controls to ensure that differences were not due to batch effects, cell cycle stage or sample quality. Clustering of single cells across all samples indicated that gene expression profiles are similar, confirming reproducibility. Gene ontology analysis of differentially expressed genes between cells with and without RKIP overexpression reveals gene sets that are important in tumor cell transitions from metastatic to non-metastatic states. These data will allow us to specifically test whether metastatic tumors are more heterogeneous than non-metastatic tumors in TNBC. Citation Format: Dongbo Yang, Christopher Dann, Sebastian Pott, Marsha Rosner. Characterizing mechanisms for inhibiting metastasis in triple negative breast cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-030.