Selectively-Packaged Proteins in Breast Cancer Extracellular Vesicles Involved in Metastasis

Abstract

Cancer-derived extracellular vesicles are known to play a role in the progression of the disease. In this rapidly-growing field, there are many reports of phenotypic changes in cells following exposure to cancer-derived extracellular vesicles. This study examines the protein contents of vesicles derived from three well-known breast cancer cell lines, MCF-7, MDA-MB-231 and T47D, using peptide-centric LC-MS/MS and cytokine multiplex immunoassay analysis to understand the molecular basis of these changes. Through these techniques a large number of proteins within these vesicles were identified. A large proportion of these proteins are known to be important in cancer formation and progression and associated with cancer signaling, angiogenesis, metastasis and invasion and immune regulation. This highlights the importance of extracellular vesicles (EVs) in cancer communications and shows some of the mechanisms the vesicles use to assist in cancer progression.

A Molecular Analysis of Cytokine Content across Extracellular Vesicles, Secretions, and Intracellular Space from Different Site-Specific Adipose-Derived Stem Cells

“…Extracellular vesicles (EVs) have gained substantial traction in recent years due to the cargo they envelope and transport between cells [ 24 ]. Recent studies have indicated the EV cargo is selectively packaged and not a random grouping of local molecules as a waste removal mechanism [ 10 , 11 ].…”

“…EVs were isolated similarly to the procedure outlined in Dalla et al [ 11 ], where growth medium was collected from each ADSC cell sample (abdomen, thigh, and chin), and EVs were isolated by differential centrifugation. Media from each cell sample was centrifuged at 20,000× g for 1 h at 4 °C to pellet EVs.…”

“…Alternate routes and modes of cytokine delivery and translocation have been investigated including active transport. There is mounting evidence that various molecules, including arrays of proteins, peptides, and cytokines, are selectively packaged into extracellular vesicles (EVs) [ 10 , 11 , 12 ]. The EV cytokine cargo can be delivered to the intracellular space by membrane and EV fusion events, allowing cytokine uptake and subsequent interaction with nuclear receptor pathway components [ 13 ].…”

The Role and Application of Salivary Exosomes in Malignant Neoplasms

“…Lau et al established an in vitro model of breast cancer and found through microarray analysis that exosomes derived from breast cancer cells could process the transcription of salivary exosomes, thereby changing the content of the salivary exosome. 42 In a mouse model, exosomes secreted by pancreatic cancer cells were able to regulate the transcription of genes in the saliva, and further, pancreatic cancer-specific transcriptional genes were identified as having increased expression in salivary exosomes, indicating the presence of markers of pancreatic cancer cells in salivary exosomes. 43 Sun et al used quantitative methods to compare the salivary exosome proteomics profile of normal subjects and patients with lung cancer, and confirmed that four proteins (BPIFA1, CRNN, MUC5B, and IQGAP) derived from lung tissue cells and could be used for non-invasive detection of lung cancer, and further, approximately 80% of the proteins in salivary exosomes and serum exosomes were shared.…”

Impact of Medium-Sized Extracellular Vesicles on the Transduction Efficiency of Adeno-Associated Viruses in Neuronal and Primary Astrocyte Cell Cultures

“…In addition to their physiological roles, EVs may also play an important role in several pathological conditions [ 27 ]. Therefore, they have attracted increasing attention as biomarkers [ 28 , 29 , 30 , 31 ] in the past few years. Moreover, EVs are also promising therapeutic tools.…”