Abstract 1084: Triple-negative breast cancer displays a unique subset of macrophages dependent on CCL5 signaling

Abstract

Abstract Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer. While five-year survival rates have reached 98% in patients treated with anti-ER or anti-HER2 therapies, patients with TNBC have a five-year survival rate of only 24%. Currently, the only form of therapy for these patients is surgery and platinum based chemotherapy. However, patient outcome is generally poor. Additionally, this disease disproportionately affects African-American women and lower income women, with rates seen approximately three times higher in African-American women compared to the rest of the population. An alternative strategy for treating TNBC patients involves targeting the tumor stroma. Here we have used an RNA sequencing approach that utilizes species information to precisely resolve tumor- and stroma-specific gene expression in a xenograft system. We employed a triple-negative breast cancer (TNBC) model in which primary tumor invasiveness is controlled by the metastasis suppressor Raf Kinase Inhibitory Protein (RKIP). RKIP expression, which converts invasive tumors to noninvasive tumors, dramatically inhibits macrophage infiltration. The mechanism, which is dependent on Let-7 suppression of HMGA2, involves decreased expression of the chemokine CCL5. Furthermore, overexpression of CCL5 partially rescued the infiltration of macrophages into the tumor and intravasation of tumor cells into the blood stream. MALDI-TOF mass spectrometry was used to characterize the TNBC-infiltrating macrophages. Together, these studies identify targetable pathways involving tumor-macrophage crosstalk that potentiate TNBC cell invasion and metastasis. Citation Format: Daniel C. Rabe, Casey Frankenberger, Russell Bainer, Yoav Gilad, Marsha Rich Rosner. Triple-negative breast cancer displays a unique subset of macrophages dependent on CCL5 signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1084. doi:10.1158/1538-7445.AM2014-1084