Akademik Veri Yönetim Sistemi
10. Multidisipliner Kanser Araştırma Kongresi, Eskişehir, Türkiye, 8 - 11 Mayıs 2025, ss.1, (Özet Bildiri)
Introduction and Aim: Pancreatic
cancer is low survival rates and high metastatic potential. One of the main
reasons for treatment failure is the dense desmoplastic microenvironment of the
tumor. Mesenchymal stem cells(MSCs) can affect the tumor microenvironment by
secreting molecules. While some studies suggest that MSCs have antitumorigenic
effects, others suggest that they may promote tumor progression. In this study,
we investigate the effects of both naïve MSCs and TLR3-induced or inhibited MSC
phenotypes on apoptosis, cell cycle and expression of tumor-associated genes in
Panc-1 cells.
Materials and Methods: Adipose-derived
MSCs were treated with a TLR3 agonist(0.5 µg/ml) and antagonist(1 µg/ml) based
on cytokine (IL-6, TNF-α, IL-1β, IL-1α, IL-10, and TGF-β) gene expression
responses. In an indirect co-culture model using 0.4 μm inserts, Panc-1 cells
were cultured with MSCs at a 1:10 ratio. Apoptosis, cell cycle, and gene
expression analyses were performed at 72 hours.
Results :At the
end of 72h, apoptosis was highest in the TLR3-stimulated MSC-Panc-1 group(44%)
and lowest in the Panc-1 group (25%). The percentage of cells in the G1 phase
increased in the naïve(61.4%) and TLR3-stimulated MSC-Panc-1 groups(61.8%)
compared to the Panc-1 group(51.6%). In naïve and TLR3-stimulated MSCs,
CD44,ZEB1, and VIM expression in Panc-1 cells was downregulated, while CDH1 and
CLDN1 were upregulated. MMP2 and MMP9 were downregulated in all groups, whereas
TIMP1,PLAU, and VEGFR2 were upregulated.
Discussion: The
effects of MSCs on cancer cells remain controversial in the literature.
Pro-inflammatory MSCs (MSC1) have been shown to have antitumor properties and
anti-inflammatory MSCs (MSC2) have been shown to have protumor properties.
However, in co-culture studies, this effect was most pronounced at a ratio of
(Panc-1)10:1(MSC). Understanding the role of MSCs in the tumor microenvironment
will provide insights for the development of future microenvironment-targeted
therapeutic approaches.
Keywords:
Pancreatic cancer, Mesenchymal stem cells,
TLR3, tumor microenvironment, MSC2.
This study was supported by TUBITAK-1002 with
project number 124S740.