Abstract
Abstract The discovery of a feasible and specific biomarkers is required for early detection of breast cancer. Breast cancer secretes microvesicles (MV) in large quantities to blood circulation to communicate with distant cells such as immune cells to support tumor growth and prepare the metastatic niche. Our recent studies detected a specific peptide from the a2 isoform vacuolar ATPase (a2NTD) as a component of the MV of breast cancer cells and not from MV of normal mammary epithelial cells. a2NTD expression positively correlates with the invasiveness of breast cancer cells, modulates immune cells, and promotes tumor growth, and metastasis. Detection of a2NTD in liquid biopsies and determination of its regulatory role will offer a feasible and specific biomarker for breast cancer. We revealed that a2NTD were highly expressed in exosomes isolated from plasma of breast cancer patients (BC-Ex) in comparison to isolated exosomes from normal donors (N-Ex). BC-Ex induces the gene expression and the secretion of cancer promoting factors from PBMCs such as IL-8, MCP-1, TNF-α and MMP-9 relative to vehicle control or N-Ex. Angiogenesis assay showed that secreted factors from BC-Ex treated PBMCs promote tube formation in HUVEC cell line. In addition, 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 and the release of Arg-1 suggesting that a2NTD reprograms neutrophils to have immunosuppressive phenotype. Together, this data shows that a2NTD can be a potential predictor of the growth and metastasis of breast cancer. Citation Format: Safaa A. Ibrahim, Valerie Riehl, Kenneth D. Beaman. Novel breast cancer biomarker in liquid biopsies and its immune regulatory role [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 460.
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