Abstract
Tumor-derived extracellular vesicles (EVs), including exosomes, contain proteins that mirror the molecular landscape of producer cells. Being potentially detectible in biological fluids, EVs are of great interest for the screening of cancer biomarkers. To reveal universal, tissue-specific, and line-specific markers, we performed label-free mass spectrometric profiling of EVs originating from the human colon cancer cell lines Caco-2, HT29, and HCT-116, as well as from the lung cancer cell lines NCI-H23 and A549. A total of 651 proteins was identified in the EV samples using at least two peptides. These proteins were highly enriched in exosome markers. We found 11 universal, eight tissue-specific, and 29 line-specific markers, the levels of which were increased in EVs compared to the whole lysates. The EV proteins were involved in the EGFR, Rap1, integrin, and microRNA signaling associated with metastasis and cancer progression. An EV protein-based assay could be developed as a liquid biopsy tool.
Highlights
According to the World Health Organization (WHO) data for 2018, lung cancer (LC) and colorectal cancer (CRC) are the most common causes of cancer-related deaths worldwide, accounting for an estimated 1.76 million and 862,000 deaths, respectively
Mass spectrometric analysis of the extracellular vesicles (EVs) derived from lung cancer and colorectal cancer cells resulted in the identification of 850 proteins in all EV samples studied
Most EV proteins within the annotation groups, even in the small-sized groups, were enriched in their interactions according to the STRING analysis. These results suggest that EVs regulate the oncogenic pathways, i.e., EGFR, Ras-associated protein-1 (Rap1), integrins, and MicroRNA signaling, and can contribute to metastasis and cancer progression in such a way
Summary
According to the World Health Organization (WHO) data for 2018, lung cancer (LC) and colorectal cancer (CRC) are the most common causes of cancer-related deaths worldwide, accounting for an estimated 1.76 million and 862,000 deaths, respectively. They rank first (2.09 million cases) and third (1.80 million cases) in terms of occurrence (https://www.who.int/news-room/fact-sheets/detail/cancer). Computed tomography (CT)-guided lung biopsy and flexible bronchoscopy are the most common diagnostic procedures [5]. Their main complications include pneumothorax (20–25% of cases) and pulmonary hemorrhaging (41.1%), which in rare cases can be severe. Depending on the patient’s characteristics, less invasive but less sensitive methods of LC diagnosis (e.g., sputum cytology) are preferred
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