Poster Session II. - B: Molecular Medicine
Ms. Németh Afrodité
B4Y9EK
Pázmány Péter Catholic University
+36202800061
nemeth.afrodite@itk.ppke.hu
EV pretreatment enhances melanoma cell migration despite dual MAPK pathway inhibition
Afrodité Németh1, Alexandra Simon1, Gréta Lilla Bányai1, Tamás Márton Garay2
1: Pázmány Péter Catholic University
2: Pázmány Péter Catholic University, Semmelweis University
Poszter
Poster Session II. - B: Molecular Medicine
English
Molecular Medicine
Introduction:
Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles released by all cell types, playing key roles in intercellular communication and cancer progression. In previous work, we found that EVs promote melanoma cell migration even under BRAF inhibitor (BRAFi) treatment. However, this effect was diminished when MEK inhibitors (MEKi) were combined with BRAFi, possibly because those cell lines were not exposed to MEKi previously. To address this, we developed a melanoma cell line resistant to both encorafenib (BRAFi) and binimetinib (MEKi) to study EVs involvement in resistance.
Methods:
Resistant clones were generated by long-term low-dose drug exposure and validated by SRB assays. Morphology and behavior were assessed via videomicroscopy, proliferation via cell counting, and migration through semi-automated tracking with CellTracker. EVs were isolated from both sensitive and resistant cells and characterized by Qubit (protein), SPV (lipid), and NTA (particle content and size). EVs effects were tested using two strategies: (1) co-treatment with drugs and EVs, and (2) EV pretreatment 24 hours prior to drug exposure.
Results:
Resistant cells showed altered morphology resembling epithelial-to-mesenchymal transition (EMT), with elongation and decreased circularity. Their proliferation and migration were reduced, while the produced EVs’ lipid content was significantly elevated. EVs treatment did not increased cell proliferation under BRAFi-MEKi treatment, however, EV pretreatment enhanced migration under dual drug pressure. Simultaneous EV-drug treatment failed to show such effect.
Conclusion:
These results suggest that EVs contribute to therapy resistance not only through binding or encapsulating the drug but also by transferring complex signals that modulate cell behavior over time. The enhanced migration following EV pretreatment implies a potential role in metastasis even under targeted therapy.
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Pázmány Péter Catholic University
Dr. Tamás Márton Garay
I give consent to the publication of my abstract on the website of the congress.
in doctoral studies after complex exam (PhD)
Szabad
elfogadva
poszter
nem rendelkezett róla
9045
19:12
19:18