Different exosome cargo from plasma/bronchoalveolar lavage in non‐small‐cell lung cancer

Abstract

Tumor-derived exosomes mediate tumorigenesis by facilitating tumor growth, metastasis, development of drug resistance, and immunosuppression. However, little is known about the exosomes isolated from bronchoalveolar lavage (BAL) in patients with lung neoplasm. Exosomes isolated in plasma and BAL from 30 and 75 patients with tumor and nontumor pathology were quantified by acetylcholinesterase activity and characterized by Western Blot, Electron Microscopy, and Nanoparticle Tracking Analysis. Differences in exosome cargo were analyzed by miRNA quantitative PCR in pooled samples and validated in a second series of patients. More exosomes were detected in plasma than in BAL in both groups (P < 0.001). The most miRNAs evaluated by PCR array were detected in tumor plasma, tumor BAL, and nontumor BAL pools, but only 56% were detected in the nontumor plasma pool. Comparing the top miRNAs with the highest levels detected in each pool, we found close homology only between the BAL samples of the two pathologies. In tumor plasma, we found a higher percentage of miRNAs with increased levels than in tumor BAL or in nontumor plasma. The data reveal differences between BAL and plasma exosome amount and miRNA content.

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

“…which may be potentially significant to the development of a new class of non-invasive diagnostic tests based on extracellular nucleic acids. Accordingly, tumour- related miRNAs have been found in bronchoalveolar lavage fluid [57,58], pleural effusion fluid [59,60] and blood plasma/serum [15,51,61] from lung cancer patients. The mechanisms of how miRNAs can be released from cells include both cell death (necrosis and apoptosis) and active secretion [62].…”

Challenges and Strategies in Precision Medicine for Non-Small-Cell Lung Cancer

“…In the case of lung cancer, the most common EGFR mutations or ALK rearrangements, patients have benefits with TKI treatment such as afatinib, gefinib, elotinib, crizotinib, and ceritinib [126,127]. Unfortunately, these benefits to treatment are short-lived due to acquired resistance to treatment [128,129].…”

“…Exosomes are believed to provide the first communication network between tumour cells, its microenvironment and at distal sites transported by the blood circulation. In NSCLC patients, they can be detected in many body fluids including the plasma and bronchoalveolar lavage [126]. Their function may change during the progression of cancer in the earlier stages they could provide a means to evade immune detection, providing nutrient support from the microenvironment through release of growth factors and a communication system at later stages crucial for assisting the metastatic process [127].…”

Exosomes: potential model for complement-stealth delivery systems

“…In pancreatic cancer, the protein and microRNA content of tumor-specific exosomes can be analyzed in order to increase the effectiveness of diagnosis and complement available diagnostic strategies (66). Exosomes that contain different cargos and receptors, like epidermal growth factor receptor, in their structure can be used in the diagnosis of lung cancer (67,68).…”