Abstract 2102: UFH-001: A novel triple-negative, CAIX-positive cell line for small-molecule targeting of human breast cancer

Specific treatment options for patients with metastatic breast cancers, especially of the triple negative subtype (TNBC), are limited and most patients develop resistance to radiation and/or chemotherapy. Because of this, the mortality rate in women with TNBC remains high. Carbonic anhydrases (CAs), most specifically membrane-bound CAIX, has been shown to play an important role in tumor progression and as a result is validated as a therapeutic target in several aggressive cancers. In breast cancer, CAIX expression has been shown to be ubiquitous in hypoxic TNBC tissues and is considered a prognostic marker and a potential therapeutic target. Therefore targeting CAIX activity, using small molecule inhibitors, in these highly aggressive and metastatic TNBCs may serve to improve overall disease free survival and therapeutic outcome in clinics. Our goal for this study was to 1) Identify and/or develop a cell line that expresses CAIX in a hypoxia independent manner and is representative of TNBCs and 2) To target CAIX activity in this cell line and observe the effects of CAIX inhibition on its growth and metastasis. Our hypothesis is that CAIX inhibition, in the context of a hypoxic and/or acidic microenvironment, will dysregulate its ability to maintain the acidic pH preferred by cancer cells which favors their growth and migration. To achieve our aims, we newly developed and characterized an endogenous CAIX-expressing cell line named UFH-001. Our results show that CAIX expression and activity in this cell line, although endogenous under normoxic conditions, is increased more than 2 fold under hypoxic conditions. This cell line is also representative of TNBCs (ER/PR and HER2 negative) with a more epithelial-like morphology and phenotype. UFH-001 cells grow aggressively and have the ability to migrate/invade and form tumors in vivo. In these studies we have also shown how inhibition of CAIX activity, using sulfonamide-based inhibitors, affects UFH-001 growth in an apoptosis independent manner and decrease the migratory/inhibitory capacity of these cells. Taken together, our observations indicate that CAIX is a viable small molecular drug target for the treatment of patients with TNBCs. Citation Format: Mam Y. Mboge, Zhijuan Chen, Lingbao Ai, Chingkuang Tu, Fabrizio Carta, Claudiu Supuran, Christopher J. Frost, Zaihui Zhang, Robert McKenna, Coy Heldermon, Susan C. Frost. UFH-001: A novel triple-negative, CAIX-positive cell line for small-molecule targeting of human breast cancer [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 2102.