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Review
. 2018 Mar 2;10:131-141.
doi: 10.1016/j.omtn.2017.11.014. Epub 2017 Dec 1.

Exosomes in Cancer Liquid Biopsy: A Focus on Breast Cancer

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Free PMC article
Review

Exosomes in Cancer Liquid Biopsy: A Focus on Breast Cancer

Sina Halvaei et al. Mol Ther Nucleic Acids. .
Free PMC article

Abstract

The important challenge about cancer is diagnosis in primary stages and proper treatment. Although classical clinico-pathological features of the tumor have major prognostic value, the advances in diagnosis and treatment are indebted to discovery of molecular biomarkers and control of cancer in the pre-invasive state. Moreover, the efficiency of available therapeutic options is highly diminished, and chemotherapy is still the main treatment due to lack of enough specific targets. Accordingly, finding the new noninvasive biomarkers for cancer is still an important clinical challenge that is not achieved yet. There are current technologies to screen, diagnose, prognose, and treat cancer, but the limitations of these implements and procedures are undeniable. Liquid biopsy as a noninvasive method has a promising future in the field of cancer, and exosomes as one of the recent areas have drawn much attention. In this review, the potential capability of exosomes is summarized in cancer with the special focus on breast cancer as the second cause of cancer mortality in women all around the world. It discusses reasons to choose exosomes for liquid biopsy and the studies related to different potential biomarkers found in the exosomes. Moreover, exosome studies on milk as a specific biofluid are also discussed. At last, because choosing the method for exosome studies is very challenging, a summary of different techniques is provided.

Keywords: application; bio-fluids; biofluid; breast milk; clinical; exosome; extracellular vesicles.

Figures

Figure 1
Figure 1
Schematic Representation of TNBC Exosomes TNBC exosomes represent some surface proteins, including CD98, CD147, and CD59, and some overexpressed miRNAs (miR-134, miR-21, miR-373, and miR-1246).
Figure 2
Figure 2
Proposed Exosomes’ Role in BC Treatment (A) miR-134 transfected Hs578Ts cells released miR-134-carrying exosomes that can downregulate STAT5B and HSP90 expression. Also, these exosomes reduce migration and invasion, and increase anti-HSP90 drug sensitivity in secondary Hs578Ts cells. (B) Human umbilical vein endothelial (HUVE) cells released miR-503-overexpressing exosomes after PTX and EPB treatment. These exosomes had the potential to reduce BC invasion and cyclin D2 and D3 expression that led to decline in BC cells proliferation. (C) Human embryonic kidney cells (HEK239) were transfected with GE11 protein (specifically binds to EGFR-expressing cells) and let-7a miRNA. HEK239 cells released GE11-expressing and let-7a-overexpressing exosomes, which bind specifically to EGFR-expressing xenograft BC tissues, and inhibited tumor development in animal model.
Figure 3
Figure 3
Proposed Exosomes’ Role in BC Resistance to Therapy (A) Tamoxifen-resistant BC cells (LCC2 cell line) secrete UCA1-overexpressed exosomes, which can cause resistance to tamoxifen (TAM) treatment of the MCF7 cell line and decrease apoptosis through reduction of cleaved caspase-3 expression. (B) RAB27B-upregulated stromal cells release exosomes that contain 5′-triphosphate RNAs and activate STAT1-dependent antiviral signaling and NOTCH3 pathways in adjacent BC cells. The crosstalk between these two signaling pathways results in reduction of chemo-resistance and radiotherapy (RT) resistance in different BC cell lines.

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