Abstract LB-C08: Exploring glycan markers for immunotyping and precision-targeting of breast circulating tumor cells (CTCs)

Abstract

Abstract Recognition of abnormal glycosylation in virtually every cancer type has raised great interest in exploration of the tumor glycome for biomarker discovery. Identifying glycan markers of circulating tumor cells (CTCs) represents a new development in tumor biomarker discovery. The aim of this study was to establish an experimental approach to enable rapid screening of CTCs for glycan marker identification and characterization. We applied carbohydrate microarrays and a high-speed fiber-optic array scanning technology (FASTcell) to explore potential glycan markers of breast CTCs (bCTCs) and targeting antibodies. An anti-tumor monoclonal antibody, HAE3-C1 (C1), was identified as a key immunological probe in this study. In our carbohydrate microarray analysis, C1 was found to be highly specific for an O-glycan cryptic epitope, gpC1. Using FASTcell technology, we established a procedure to quantify expression levels of gpC1 in tumor cells. In blood samples from five Stage IV metastatic breast cancer patients, the gpC1 positive CTCs were detected in all subjects; approximately 40% of bCTCs were strongly gpC1 positive. Interestingly, the CTCs from a triple-negative breast cancer patient with multiple sites of metastasis were predominantly gpC1 positive (92.5%, 37/40 CTCs). Taken together, we present here a practical approach to examine rare cell expression of glycan markers. Using this approach, we identified an O-core glyco-determinant gpC1 as a potential immunological target of bCTCs. Given its bCTC-expression profile, this target warrants an extended investigation in a larger cohort of breast cancer patients. Citation Format: Lidia C. Sambucetti, Xiaohe Liu, Ben Hsieh, Richard Bruce, George Somlo, Jiaoti Huang, Denong Wang. Exploring glycan markers for immunotyping and precision-targeting of breast circulating tumor cells (CTCs). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-C08.