Extracellular vesicles promote migration despite BRAF inhibitor treatment in malignant melanoma cells.

Németh, Afrodité [Németh, Afrodité (biológia), author] Roska Tamás Műszaki és Természettudományi Dokto... (PPCU / ITK); Bányai, Gréta L [Bányai, Gréta Lilla (biológia), author] Roska Tamás Műszaki és Természettudományi Dokto... (PPCU / ITK); Dobos, Nikolett K; Kós, Tamás; Gaál, Anikó [Gaál, Anikó (analitikai kémia), author] BNK (IMEC); Varga, Zoltán [Varga, Zoltán (biofizika, kolloi...), author] BNK (IMEC); Institute of Materials and Environmental Chemistry; Buzás, Edit I [Buzás, Edit Irén (Immunbiológia), author] Department of Genetics, Cell- and Immunology (SU / FM / I); ELKH-SE Translational Extracellular Vesicle Res... (SU / FM / I / DGCI); HCEMM-SU Extracellular Vesicles Research Group (SU / FM / I / DGCI); Khamari, Delaram [Khamari, Delaram (Extracellular ves...), author] Department of Genetics, Cell- and Immunology (SU / FM / I); Dank, Magdolna [Dank, Magdolna (onkológia), author] Department of Internal Medicine and Oncology (SU / FM / C); Takács, István [Takács, István (Endokrinológia), author] Department of Internal Medicine and Oncology (SU / FM / C); Szász, A Marcell [Szász, Attila Marcell (emlőpatologia), author] Department of Internal Medicine and Oncology (SU / FM / C); Garay, Tamás ✉ [Garay, Tamás (sejtbiológia, tum...), author] Department of Internal Medicine and Oncology (SU / FM / C)

English Article (Journal Article) Scientific
Published: CELL COMMUNICATION AND SIGNALING 1478-811X 1478-811X 22 (1) Paper: 282 , 14 p. 2024
  • SJR Scopus - Biochemistry: D1
Identifiers
Fundings:
  • Thematic Excellence Program(TKP2021-EGA-42)
Subjects:
  • Clinical medicine
Extracellular vesicles (EVs) constitute a vital component of intercellular communication, exerting significant influence on metastasis formation and drug resistance mechanisms. Malignant melanoma (MM) is one of the deadliest forms of skin cancers, because of its high metastatic potential and often acquired resistance to oncotherapies. The prevalence of BRAF mutations in MM underscores the importance of BRAF-targeted therapies, such as vemurafenib and dabrafenib, alone or in combination with the MEK inhibitor, trametinib. This study aimed to elucidate the involvement of EVs in MM progression and ascertain whether EV-mediated metastasis promotion persists during single agent BRAF (vemurafenib, dabrafenib), or MEK (trametinib) and combined BRAF/MEK (dabrafenib/trametinib) inhibition.Using five pairs of syngeneic melanoma cell lines, we assessed the impact of EVs - isolated from their respective supernatants - on melanoma cell proliferation and migration. Cell viability and spheroid growth assays were employed to evaluate proliferation, while migration was analyzed through mean squared displacement (MSD) and total traveled distance (TTD) measurements derived from video microscopy and single-cell tracking.Our results indicate that while EV treatments had remarkable promoting effect on cell migration, they exerted only a modest effect on cell proliferation and spheroid growth. Notably, EVs demonstrated the ability to mitigate the inhibitory effects of BRAF inhibitors, albeit they were ineffective against a MEK inhibitor and the combination of BRAF/MEK inhibitors. In summary, our findings contribute to the understanding of the intricate role played by EVs in tumor progression, metastasis, and drug resistance in MM.
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2025-03-18 03:25