Extracellular vesicles promote migration despite BRAF inhibitor treatment in malignant melanoma cells.
Melanoma
/ pathology
Extracellular Vesicles
/ metabolism
Proto-Oncogene Proteins B-raf
/ metabolism
Humans
Cell Movement
/ drug effects
Cell Line, Tumor
Protein Kinase Inhibitors
/ pharmacology
Cell Proliferation
/ drug effects
Vemurafenib
/ pharmacology
Pyrimidinones
/ pharmacology
Pyridones
/ pharmacology
Imidazoles
/ pharmacology
Oximes
/ pharmacology
Cell migration
Dabrafenib
Extracellular vesicles
Melanoma
Single cell tracking
Trametinib
Vemurafenib
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
22 May 2024
22 May 2024
Historique:
received:
14
08
2023
accepted:
10
05
2024
medline:
23
5
2024
pubmed:
23
5
2024
entrez:
22
5
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38778340
doi: 10.1186/s12964-024-01660-4
pii: 10.1186/s12964-024-01660-4
doi:
Substances chimiques
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Protein Kinase Inhibitors
0
trametinib
33E86K87QN
dabrafenib
QGP4HA4G1B
Vemurafenib
207SMY3FQT
Pyrimidinones
0
Pyridones
0
Imidazoles
0
Oximes
0
BRAF protein, human
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
282Subventions
Organisme : National Research, Development and Innovation Office
ID : TKP2021-EGA-42
Organisme : National Research, Development and Innovation Office
ID : TKP2021-EGA-42
Organisme : National Research, Development and Innovation Office
ID : TKP2021-EGA-42
Organisme : National Research, Development and Innovation Office
ID : TKP2021-EGA-42
Organisme : National Research, Development and Innovation Office
ID : TKP2021-EGA-42
Organisme : National Research, Development and Innovation Office
ID : TKP2021-EGA-42
Informations de copyright
© 2024. The Author(s).
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