Exosomes are major contributors in cell to cell communication due to their ability to transfer biological material such as protein, RNA, DNA, and miRNA. Additionally, they play a role in tumor initiation, promotion, and progression, and recently, they have emerged as a potential source of information on tumor detection and may be useful as diagnostic, prognostic, and predictive tools. This review focuses on exosomes from lung cancer with a focus on EGFR mutations. Here, we outline the role of exosomes and their functional effect in carcinogenesis, tumor progression, and metastasis. Finally, we discuss the possibility of exosomes as novel biomarkers in early detection, diagnosis, assessment of prognosis, and prediction of therapeutic response in EGFR-mutated lung cancer.

Exosomes, a class of extra cellular nano-sized vesicles (EVs), and their contents have gained attention as potential sources of information on tumor detection and regulatory drivers of tumor progression and metastasis. The effect of exosomes isolated from patients with an Epidermal Growth Factor Receptor (EGFR)-mutated adenocarcinoma on the promotion of epithelial–mesenchymal transition (EMT) and invasion were examined. Exosomes derived from serum of patients with EGFR-mutated non-small cell lung cancer (NSCLC) mediate the activation of the Phosphoinositide 3-kinase (PI3K)/AKT/ mammalian target of rapamycin (mTOR) pathway and induce an invasion through the up-regulation of matrix metalloproteinase-9 (MMP-9) in A549 cells. We observed a significant increase in the expression of vimentin, a mesenchymal marker, while retaining the epithelial characteristics, as evidenced by the unaltered levels of E-cadherin and Epithelial cell adhesion molecule (EPCAM). We also observed an increase of nuclear factor erythroid 2-related factor 2 (NFR2) and P-cadherin expression, markers of hybrid EMT. Exosomes derived from EGFR-mutated adenocarcinoma serum could be a potential mediator of hybrid EMT and tumor invasion. Understanding how cancerous cells communicate and interact with their environment via exosomes will improve our understanding of lung cancer progression and metastasis formation.

There is marked sexual dimorphism in the development and progression of pulmonary hypertension. We show differences in RNA and protein expression between female and male human pulmonary microvascular endothelial cells grown under conditions of physiological shear stress, which identify sex-different cellular pathways both in normoxia and hypoxia. Importantly, these differences were detected in the absence of sex hormone differences. The pathways identified may provide novel targets for the development of sex-specific therapies.

Exosomes are a class of extra cellular vesicles (EVs), with a multi vesicular endosomal origin, that are released by all cell types, with sizes ranging from 30-100nm and a lipid bilayer membrane. Exosomes and their contents have emerged as a potential source of information on tumour detection and regulatory drivers of tumour progression and metastasis. They have been reported to influence epithelial mesenchymal transition (EMT) in pathological states such as metastatic lung cancer. We analysed the effects of exosomes derived from serum of different lung cancer patients: Epidermal Growth Factor Receptor (EGFR)-mutated adenocarcinoma (N=6), wild-type adenocarcinoma (N=3), squamous (N=1) and serum of patient with no cancer (N=1) on cells from an A549 cell line. We observed by zymography, that all exosomes, regardless of patient origin, induced an increase in MMP2 activity in all A549 cells treated compared to the non-treated cells. However, the increase of pro-MMP9 and MMP9 activity was seen only in A549 cells treated with exosomes derived from EGFR-mutated adenocarcinoma patients (respectively a fold increase of 54 and 37 compared to the non-treated cells). MMPs are one of the major attributes that epithelial cells acquire after undergoing EMT. Our results suggest that exosomes derived from EGFR-mutated adenocarcinoma serum could be a potential mediator of EMT and tumour invasion and may provide insights into the mechanisms of lung cancer progression and metastasis. However, additional studies are required to precisely delineate these mechanisms.