TAMI-04. OLFACTORY RECEPTOR 5B21 DRIVES BREAST CANCER BRAIN METASTASIS THROUGH STAT3/NFΚB/CEBPΒ PATHWAY

Abstract

Abstract Olfactory receptors (ORs), responsible for the sense of smell, play an essential role in various physiological processes outside the nasal epithelium, including cancer. In breast cancer, however, the expression and function of ORs remain understudied. We established a breast cancer metastasis model by intracardiac injection of MDA-MB-231 (231P) in immunocompromised mice and produced a series of derivative cell lines from developed metastatic sites, including the brain-seeking clone (231Br). We examined the significance of ORs transcript abundance in primary and metastatic breast cancer to different tissues, including the brain, bone, and lung. While 20 OR transcripts were differentially expressed in distant metastases, OR5B21 displayed high expression in all three metastatic sites with respect to the primary tumor, especially in brain metastasis with 13 fold higher than the primary site. Metastatic clones showed distinguishing higher invasion biological characteristics compared to parental cells in vivo and in vitro. Knockdown of OR5B21 significantly decreased the invasion and migration of MDA-MB-231 Brain-seeking metastatic cell as well as metastasis to different organs, including the brain, while overexpression of OR5B21 had the opposite effect. Mechanistically, OR5B21 expression was associated with epithelial to mesenchymal transition through the STAT3/NFkB/CEBPβ signaling pathway. We propose OR5B21 (and potentially other ORs) as a novel oncogene contributing to breast cancer brain metastasis and a potential target for adjuvant therapy.