Abstract 399: Nanoparticle silencing of β1 and β3 integrins augments Dasatinib sensitivity

Abstract

Abstract Triple negative breast cancers (TNBCs) are an aggressive subcategory of breast cancers that currently lack FDA-approved targeted therapies. Previous studies have i) further subcategorized TNBCs into 5 distinct subtypes, each with a preferential response to specific chemotherapies and ii) identified beta1 and beta3 integrins to be key mediators of breast cancer EMT and metastasis. We surveyed beta1 and beta3 integrin expression in the 5 subtypes of TNBC with and without treatment of their proposed chemotherapies by western blot analysis. Using nanoparticles, we delivered beta1 and beta3 integrin-specific siRNAs to silence the expression of both integrins either with or without treatment of the proposed chemotherapies, and evaluated the effect of these treatment regimens on EMT, invasion, and 3D outgrowth. We demonstrated that beta1 and beta3 integrins are robustly expressed in the Mesenchymal Stem-Like, Mesenchymal, and Basal-Like2 subtypes of TNBCs. Furthermore, we observed elevated expression of beta1 integrin upon Dasatinib treatment of the Mesenchymal Stem-Like subtype. Lastly, we determined that delivery of beta1 and beta3 integrin siRNAs sensitized breast cancer cells to Dasatinib treatment. Collectively, our data suggests that delivery of beta1 and beta3 integrin-specific siRNAs in combination with Dasatinib treatment efficiently eliminates the aggressive characteristics of Mesenchymal Stem-Like breast cancer cell lines. Citation Format: Jenny G. Parvani, Vinson Chu, Sarah Roelle, Zheng-Rong Lu, William Schiemann. Nanoparticle silencing of β1 and β3 integrins augments Dasatinib sensitivity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 399. doi:10.1158/1538-7445.AM2015-399