Abstract 2731: Receptor for Hyaluronan Mediated Motility (RHAMM) promotes breast cancer progression

Abstract

Abstract Breast cancer remains one of the leading causes of cancer-related death in women in the U.S. with over 40,000 deaths annually. Understanding mechanisms of breast cancer progression holds great clinical utility to individualize patient therapy and to increase our portfolio of effective treatments for the different subtypes of breast cancer. We performed a focused gene expression analysis of 120 patients across all relevant hormone receptor (HR) subtypes at our institution. Increased expression of hyaluronan mediated motility receptor (HMMR, aka RHAMM) was associated with higher Nottingham grade, lymph node metastasis, and higher stage (all p<0.01). RHAMM expression was higher in more aggressive HR subtypes (triple negative and HER2+). Unsupervised hierarchical clustering of the cohort with a 29 gene signature related to RHAMM biologic activity further supported these associations with breast cancer progression/aggressiveness. Using CRISPR/Cas9, stable RHAMM -/- MCF10DCIS cell lines were created; RHAMM deletion does not affect cell proliferation, but significantly reduces in vitro Matrigel invasion and soft agar colony formation. RHAMM knockout also diminishes invasive progression of the MCF10DCIS cells in vivo, using the mouse intraductal (MIND) xenograft model; 83% of control xenografts demonstrate tissue invasion by 6 weeks, while only 50% of RHAMM-/- xenografts show any invasive component (p=0.03). Our human and model system data indicate a role for RHAMM function in breast cancer invasion. On-going work will investigate the dependency of the invasive phenotype specifically on RHAMM-hyaluronan binding; this interaction can be pharmacologically disrupted and may represent a specific intervention to limit breast cancer invasion and potentially metastasis. Citation Format: Claire Elizabeth Daughters, Todd P. Knutson, Colleen Forster, James McCarthy, Kaylee Schwertfeger, Andrew Nelson. Receptor for Hyaluronan Mediated Motility (RHAMM) promotes breast cancer progression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2731.