Extracellular vesicles from young women’s breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach

Abstract

Background Extracellular vesicles (EVs) are small membrane particles that contribute to cancer progression and metastases by transporting biologically significant proteins and nucleic acids. They may also serve as biomarkers of various disease states or important therapeutic targets. Breast cancer EVs have the potential to change the behavior of other cells in their microenvironment. However, the proteomic content of EVs isolated from young women’s breast cancer patients and the mechanisms underlying the influence of EVs on tumor cell behavior have not yet been reported. Methods In our current translational studies, we compared the proteomic content of EVs isolated from invasive breast cancer cell lines and plasma samples from young women’s breast cancer (YWBC) patients and age-matched healthy donors using mass spectrometry. We analyzed the functionality of EVs in two dimensional tumor cell invasion assays and the gene expression changes in tumor cells after incubation with EVs. Results We found that treatment with EVs from both invasive breast cancer cell lines and plasma of YWBC patients altered the invasive properties of non-invasive breast cancer cells. Proteomics identified differences between EVs from YWBC patients and healthy donors that correlated with their altered function. Further, we identified gene expression changes in non-invasive breast cancer cells after treatment with EVs that implicate the Focal Adhesion Kinase (FAK) signaling pathway as a potential targetable pathway affected by breast cancer-derived EVs. Conclusions Our results suggest that the proteome of EVs from breast cancer patients reflects their functionality in tumor motility assays and may help elucidate the role of EVs in breast cancer progression.

Extracellular Vesicles and Hepatocellular Carcinoma: Opportunities and Challenges

“…EVs are sensory molecules for information exchange between tumor cells in the microenvironment, activating different signaling pathways and influencing the development, progression and metastasis of tumors ( 294 – 297 ). In recent years, EVs have become promising vehicles in liver disease for their low toxicity, high stability and preferential absorption ( 298 ).…”

Delineation of Pathogenomic Insights of Breast Cancer in Young Women

“…Our finding that many upregulated genes in BCYW that are also upregulated in normal breast tissues encode proteins secreted in EVs or body fluids such as urine, saliva, breast milk, and plasma is important as it raises the possibility of developing non-invasive predictive biomarkers for the general screening of younger women who are currently excluded from the guidelines to use mammography and/or individuals without predisposed breast cancer genes. Following a somewhat similar line of thinking, but in the context of prognosis, a recent study suggested differences in the nature of cargo EVs purified from the plasma of young BC patients as compared to those from healthy donors [ 76 ]. As a good percentage of breast cancers in young women are of the TNBC subtype, it would be important to understand the nature of biomaterial packed within the circulating EVs from different subtypes of BCYW.…”

Extracellular Vesicles as Drug Delivery Systems in Organ Transplantation: The Next Frontier

“…EVs are released from all cell types studied to date, including endothelial cells [ 7 , 8 ], epithelial cells [ 9 ] and mesenchymal stem cells [ 10 , 11 ]; hence, they can also be found in a number of biofluids, including blood [ 12 ], synovial fluid [ 13 ], bile [ 14 ], breast milk [ 15 ], cerebrospinal fluid [ 16 ] and urine [ 17 ]. EVs have also been implicated in a number of diseases, including cardiovascular [ 18 , 19 , 20 ] and liver diseases [ 21 , 22 ], autoimmune [ 23 ] and neurodegenerative conditions [ 24 , 25 , 26 ] and cancer [ 27 , 28 , 29 , 30 ].…”