Abstract 2844: New breast cancer protein as a potential biomarker in liquid biopsies

Abstract

Abstract The decline in breast cancer mortality over the past 2 decades is primarily the result of advances in early detection and treatment. However, the five year relative survival rate of metastatic breast cancer (MBC) patients is only 27%. This requires the need of new biomarkers for early detection of MBC. Tumors secrete microvesicles (MV) in large quantities to blood circulation in order to communicate with distant cells such as immune cells and prepare the metastatic niche. Our recent studies showed that MV from metastatic breast cancer cells contain a specific peptide from the a2 isoform vacuolar ATPase (a2NTD). This a2NTD is undetectable in mammary epithelial cells MV but expressed abundantly by MV produced by breast tumor cells. We have previously shown that the MV containing a2NTD modulate immune cells, promotes tumor growth, metastasis and positively correlates with the invasiveness of breast cancer cells. Identifying the role of a2NTD in regulating immune cells in liquid biopsy will provide a new biomarker for breast cancer. Treatment of whole blood from healthy volunteers with MDA MB-231 MV or recombinant a2NTD drives the neutrophil transition from High density neutrophils (HDN) to Low density neutrophils (LDN). Flow cytometrical analysis showed that LDN possess the PMN-MDSCs markers CD11b+ CD15+ CD14- CD33- HLA-DR-. In addition a2NTD treatment was associated with decreased internal staining of Arg-1 in neutrophils that suggests the release of Arg-1. This data suggest that a2NTD can reprogram neutrophils to exert immunosuppressive phenotype. Further characterization of surface markers as well as functional assays demonstrate the exact phenotype of neutrophils. Together studying the impact of a2NTD present in MV on immune alteration during metastasis can be potential predictors of the growth and metastasis of breast cancer. Citation Format: Safaa A. Ibrahim, Valerie riehl, Kenneth D. Beaman. New breast cancer protein as a potential biomarker in liquid biopsies [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 2844.