Abstract C113: Antibody microarray analysis of signaling networks regulated by the CCR9/CCL25 axis in African American and Caucasian American triple-negative breast cancer

Abstract

Abstract Therapeutic outcome of breast cancer (BrCa) is impeded due to the intratumoral heterogeneity, as well as differences among cancer-bearing individuals. Triple-negative breast cancer (TNBC) is a highly aggressive subtype that disproportionally affects African-American (AA) women. However, the molecular basis of racial disparity in therapeutic response and clinical outcome of TNBC in AA compared to Caucasian American (CA) patients is still obscure. Our group was the first to show the involvement of CCR9 and its natural ligand, CCL25 in cancer progression and therapeutic response, including BrCa. In this study, using proteomic and bioinformatics approach we have quantified the race-specific differences in biologic pathways modulated by the CCR9/CCL25 in TNBC cells. The difference in signaling cascades following CCR9 activation by CCL25 in BrCa cell derived from AA and CA were determined using cancer signaling phospho-protein antibody microarray, which featured 269 antibodies. A heat map was generated to visualize differences in phosphorylation status among cell line derived from AA and CA patients, as well as differences between the cell lines after CCL25 treatment. Graphics of biologic functions and oncogenic signaling networks, which were altered by CCR9/CCL25 axis, were produced using GeneMANIA and Ingenuity Pathway Analysis (IPA) software. Cells derived from AA (MDA-MB-468), show activation/phosphorylation of GSK3α, Elk-1, p70S6K, BCL-2, MEK2, NFkB and STAT3 involved in cell survival and migration. However, cells derived from CA (MDA-MB-231) show activation/phosphorylation of VEGFR2, CTNNB1, FAK, and SHC, suggesting involvement of distinct pathway supporting cell survival following CCR9 activation. Hence, our data suggest that CCR9/CCL25 contributes to the race-specific difference in signaling pathways and these race-specific differences in the biology of TNBC could be the reasons for the disparity in disease and therapeutic outcome. Citation Format: Jeronay King Thomas, Neeraj Kapur, Hina Mir, Dominique N. Gales, James W. Lillard Jr., Shailesh Singh. Antibody microarray analysis of signaling networks regulated by the CCR9/CCL25 axis in African American and Caucasian American triple-negative breast cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C113.