LPS Stimulated MSC-Derived Extracellular Vesicles Induce Apoptosis and Cell Cycle Arrest in Pancreatic Cancer Cells

Kaçaroğlu D., Yılmaz A., Erkaya A., Şamandar Aydaş H.

2nd Extracellular Vesicles Conference (TURSEV-26), Ankara, Türkiye, 5 - 06 Haziran 2026, ss.114, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Ankara
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.114
  • Lokman Hekim Üniversitesi Adresli: Evet

Özet

Pancreatic cancer remains one of the most lethal malignancies due to challenges in early diagnosis and the limited efficacy of current

therapeutic strategies. Mesenchymal stem cells (MSCs), as key components of the tumor microenvironment, exhibit context-dependent pro- or

anti-tumorigenic effects. MSC-derived extracellular vesicles (EVs) have emerged as important mediators of intercellular communication,

capable of modulating tumor progression depending on their molecular cargo. Polarization of MSCs through Toll-like receptors, particularly

TLR4 activation, induces a phenotype (MSC1) associated with anti-tumor properties. However, the effects of EVs derived from TLR4-

stimulated MSCs on pancreatic cancer cells remain poorly understood. This study aimed to investigate the impact of EVs obtained from

lipopolysaccharide (LPS)-stimulated MSCs on pancreatic cancer cell lines. Umbilical cord-derived MSCs were cultured in serum-free medium

and stimulated with 1 μg/mL LPS. EVs were isolated from conditioned media using ultracentrifugation and ultrafiltration. Characterization

was performed by tunable resistive pulse sensing (TRPS) for size, concentration, and distribution, bicinchoninic acid (BCA) assay for protein

quantification, and flow cytometry for CD63 and CD81 expression. EVs were then applied to MiaPaCa-2 and Panc-1 pancreatic cancer cell

lines, and apoptosis and cell cycle progression were analyzed by flow cytometry. MSC-derived EVs exhibited dose-dependent cytotoxic and

anti-proliferative effects in both cell lines. In Panc-1 cells, cell viability decreased from 76.08% to 60.22%, while late apoptosis increased from

15.80% to 23.64%, reaching 29.65% following LPS-MSC EV treatment. MiaPaCa-2 cells demonstrated greater sensitivity, with viability

decreasing from 75.15% to 56.89% and late apoptosis increasing from 10.22% to 29.24%. The strongest effect was observed in the LPS-MSC

EV group (5000 EV/cell), where viability decreased to 48.01% and late apoptosis reached 37.99%. Cell cycle analysis revealed G1 phase

arrest in Panc-1 cells (increase from 56.11% to 63.29%) and G2/M phase arrest in MiaPaCa-2 cells (increase from 18.85% to ~25%). In

conclusion, MSC-derived EVs exert dose-dependent anti-tumor effects in pancreatic cancer cells, which are significantly enhanced following

LPS-mediated priming. These effects are primarily mediated through the induction of late apoptosis and cell cycle arrest. Our findings suggest

that inflammatory preconditioning enhances the therapeutic potential of MSC-derived EVs, highlighting their promise as a novel strategy for

pancreatic cancer treatment.