Identification of Developmental Endothelial Locus-1 on Circulating Extracellular Vesicles as a Novel Biomarker for Early Breast Cancer Detection

Abstract

Del-1 on circulating EVs is a promising marker to improve identification of patients with early-stage breast cancer and distinguish breast cancer from benign breast tumors and noncancerous diseases.

Isolation and Characterization of Microvesicles from Peripheral Blood

“…Levels of MVs expressing tumor-associated proteins such as MUC1, EGFR or FAK seem to be elevated in the blood of breast cancer patients 15,16 . Also for Exos, recent studies have shown that blood-derived Exos carrying tumor-specific antigens such as Glypican-1 for pancreatic cancer or Del-1 for breast cancer allow early disease detection with high specificity and sensitivity 17,18 . Additionally, serum-derived tumor Exos may contain DNA which can be used for detection of mutations such as KRAS and p53 which suggests their use for therapy prediction 19 .…”

The Potential Use of Exosomes as a Diagnostic and Prognostic Tool

“…Because of their intracellular origin, exosomes work as reporters of the biochemical changes occurring in many diseases, such as cancer, neurological or immunological conditions. Many groups managed to isolate a cell-specific population of exosomes from the blood of patients [4][5][6][7][8][9][10][11] what would allow physicians to monitor in real time the status of a patient or the efficacy of a medication by simply taking a blood sample and analyzing the content of exosomes from a specific cell-type. In addition, blood draws are carried out daily in clinical practice and they have low cost in comparison to other diagnostic methods.…”

“…The antibody-based methods use a capture antibody against an exosomal marker, either coupled to streptavidin or magnetic beads [8,11], coated on the wells of an ELISA plate [5] or used in flow cytometry separation [7]. For example, circulating glypican 1-bearing exosomes have been isolated by flow cytometry and were shown to be diagnostic for early and late pancreatic cancer [7].…”

“…Another example is the use of ELISA plates coated with an anti-CD63 antibody to capture circulating exosomes from the plasma of patients with breast cancer. When combined with a detection antibody against Del-1 protein it showed useful for diagnosis of breast cancer [5]. Also, neural exosomes from human plasma isolated with superparamagnetic microbeads coated with anti-L1CAM antibody showed higher levels of synuclein in patients with Parkinson's disease [8].…”

“…Exoquick) with an antibody-based approach [5,6]. Using this method, it was possible to discriminate between controls and AD patients by determining the levels of Aβ42 and certain phospho-specific tau species (p181 and p396) in blood-derived neural exosomes (exosomes can go across the blood brain barrier).…”