Abstract 3969: Lipocalin-2-targeted small interference RNA for inflammatory breast cancer treatment

Inflammatory Breast Cancer (IBC) is an aggressive form of invasive breast cancer with low survival rate. Available therapies to treat this type of cancer are almost limited to surgery and radiation therapy. Potential therapeutic targets for IBC treatment include the oncogene Her2 and the Epidermal Growth Factor Receptor (EGFR). However, these therapies have not been successful since not all IBC tumors are Her2-amplified and development of resistance to treatment has also been observed. Hence, there is a critical need for novel therapeutic targets for IBC treatment. One of such possibilities is Lipocalin-2 (LNC2). LCN-2 is a secreted glycoprotein and an adipokine superfamily member that posses roles in transport of small lipophilic molecules in circulation, innate immunity, and iron homeostasis. High levels of LCN2 have been observed in invasive breast cancer human tissue. Additionally, LCN2 has been linked with breast cancer tumorigenesis and metastasis. Therefore, the purpose of our study is to assess if LCN2 is a plausible therapeutic target to treat IBC. Western blot analysis was used to assess the LCN2 protein level in a panel of IBC (MDA-IBC-3, SUM-149) and non-IBC cell lines (MCF-7, MDA-MB-231, MDA-MB-438). IBC cell lines showed a significantly higher expression of the LCN2 protein in comparison to the non-IBC cell lines. We decreased the expression of the LCN2 protein with small interference RNA (siRNA) molecules. Silencing of IBC cells with LCN2-targeted siRNA molecules decreased the LCN2 protein expression levels in almost fifty percent. Colony formation assay demonstrated that siRNA-mediated LCN2 silencing in MDA-IBC-3 and SUM-149 cell lines resulted in a significant decrease in cell proliferation. Taken together these results suggest that LCN2 may become a right target for IBC treatment. Ongoing experiments include cell invasion assays to determine if LCN2-targeted siRNAs reduce the metastatic potential, increase apoptosis and block cell cycle progression. Acknowledgements: This work is supported by the University of Puerto Rico Comprehensive Cancer Center and the U54 partnership with MD Anderson Cancer Research Center. Citation Format: Ginette S. Santiago-Sanchez, Fatma Valiyeva, Bisrat Debeb, Pablo E. Mejia. Lipocalin-2-targeted small interference RNA for inflammatory breast cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3969.