Abstract B03: Stromal cells confer drug resistance to breast cancer cells in a kinetic co-culture model

Abstract

Abstract The tumor microenvironment is fundamentally involved in the response of a tumor to anti-cancer therapies. In this study, we present a novel method for kinetically measuring the proliferation of one or more cell types in mixed, co-culture models. Specifically, lentiviral based reagents are used to label nuclei of multiple cell populations within a single culture. Real time cell counts are acquired using an automated, Live Content Imaging approach in which 96-well and 384-well microplates are imaged every 2-3 hours over the course of the full 2-3 day assay. Using this strategy, we confirm data illustrating that culturing HER-2 positive breast cancer cells (SK-BR-3) in the presence of either Human Mammary Fibroblasts (HMFs) or normal skin fibroblasts (CCD-1068Sk) are resistant to the anti-proliferative and cytotoxic effects of the HER-2 and EGFR tyrosine kinase inhibitor lapatinib. Extending this data, we also completed pharmacolgical analyses, using area under the curve of the full kinetic trace, revealing nearly a 2-log difference in lapatinib sensitivity between SK-BR-3 cells grown in the presence or absence lapatinib. The data presented here reveal a novel, automated, kinetic assay for measuring proliferation of one or more cell types in mixed culture models. More importantly, these data further clarify the pharmacolgical effect stromal cells can have on the resistance of breast cancer cells to lapatinib treatment. Citation Format: Katherine Artymovich, Clare Szybut, Kalpana Patel, Tim O'Callaghan, Tim Dale, Del Trezise, Daniel M. Appledorn. Stromal cells confer drug resistance to breast cancer cells in a kinetic co-culture model. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B03.