Abstract
Background/Aim: Tyrosine kinase inhibitors (TKIs) are the first-line therapy for non-small cell lung cancer (NSCLC) patients harboring activating epidermal growth factor receptor (EGFR) mutations. Unfortunately, most patients quickly develop an acquired resistance to EGFR-TKIs. However, the effects of NSCLC harboring EGFR-T790M mutation on aggressive NSCLC phenotypes is still unclear. This study aimed to investigate the extracellular vesicles (EVs) involvement in promoting the aggressiveness of NSCLC cells. Materials and Methods: EVs were isolated from the culture media of TKI-sensitive (HCC827) and TKI-resistant (H1975) NSCLC cells using ultracentrifugation. Cell viability, proliferation, migration, and invasion were examined following incubation with indicated EVs. Results: HCC827 and H1975 cells showed time-dependent uptake of PKH67 dye labeled EVs. Incubation of EVs derived from H1975 cells (EV-H1975) did not alter the TKI sensitivity of HCC827 cells. Interestingly, EV-H1975 significantly increased HCC827 cells proliferation, invasion, and migration. By a phospho-kinase array, EV-H1975 increased phosphorylation of several proteins related to cell proliferation, invasion, and migration, including FAK, AKT, and ERK1/2, in HCC827 cells. Conclusion: EGFR-T790M NSCLC cells promote TKI-sensitive NSCLC cell aggressiveness, at least partially, through mechanisms associated with EVs.
- Received June 10, 2022.
- Revision received July 1, 2022.
- Accepted July 4, 2022.
- Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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