Akademik Veri Yönetim Sistemi
3. International Multidisciplinary Cancer Research Congress, İstanbul, Türkiye, 7 - 10 Eylül 2023, ss.69
Introduction: In order to intervene
in the dense desmoplastic tumor microenvironment, it is important to first elucidate
the interactions between cells. To investigate the potential antitumorigenic
effects of adipose-derived MSC(ADMSC) on the pancreatic ductal epithelial cell
Panc-1, we aimed to investigate the effects of both proinflammatory and
anti-inflammatory ADMSC phenotypes on EMT and metastasis.
Material and method: ADMSCs were
treated with TLR4 agonist and antagonist. Pro-inflammatory and
anti-inflammatory characters were determined according to their responses to
cytokines. An indirect co-culture model was established using 0.4 µm inserts
and Panc-1 and ADMSCs were cultured at a ratio of 1:10. Next, gene expression
levels of CDH1, VIM, ZEB1 and CLDN1 were evaluated for EMT analysis. Analysis of vimentin and E
cadherin proteins was also evaluated by immunofluorescence staining. Metastatic
potential was also analyzed by gene expressions of MMP2, KDR, PLAU, MMP9,
TIMP1, IGF2R and COL1A1.
Results: At the end of the 96h, naive
and proinflammatory ADMSCs increased the expression of CDH1 and CLDN1 of Panc-1
cells and decreased the expression of VIM gene. In metastasis related genes, it
significantly decreased the expression of MMP2, KDR, MMP9, TIMP1, IGF2R and
COL1A1 genes, except for the PLAU gene. ADMSCs with anti-inflammatory
character, showed opposite effects.
Conclusion: Both naive ADMSCs and
proinflammatory ADMSCs were showed antitumor effects on Panc-1 cells. Anti-inflammatory
ADMSCs were showed tumor promoting effects. Understanding the role of MSCs in
the tumor microenvironment will be a guiding factor for the development of
microenvironment-targeted therapeutic approaches in the future.
Keywords: Pancreatic cancer,
Mesenchymal stem cell, TLR4, Tumor microenvironment.