4.3 Article

Protein Profiling of Extracellular Vesicles Associated With Cisplatin Resistance in Lung Cancer

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ANTICANCER RESEARCH
卷 40, 期 10, 页码 5509-5516

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INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.14563

关键词

Extracellular vesicles; lung cancer; drug resistance; cisplatin; mass spectrometry

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资金

  1. Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) [16/2551-0000 286-0]
  2. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
  3. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

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Background/Aim: Extracellular vesicles (EVs) can mediate drug resistance within the tumor microenvironment by delivering bioactive molecules, including proteins. Here, we performed a comparative proteomic analysis of EVs secreted by A549 lung cancer cells and their cisplatin-resistant counterparts in order to identify proteins involved in drug resistance. Materials and Methods: Cells were co-cultivated using a transwell system to evaluate EV exchange. EVs were isolated by ultracentrifugation and analyzed using microscopy and nanoparticle tracking. EV proteome was analyzed by mass spectrometry. Results: EV-mediated communication was observed between co-cultured A549 and A549/CDDP cells. EVs isolated from both cells were mainly exosome-like structures. Extracellular matrix components, cell adhesion proteins, complement factors, histones, proteasome subunits and membrane transporters were found enriched in the EVs released by cisplatin-resistant cells. Conclusion: Proteins identified in this work may have a relevant role in modulating the chemosensitivity of the recipient cells and could represent useful biomarkers to monitor cisplatin response in lung cancer.

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