The IL-17A/IL-17RA Axis Is Not Related to Overall Survival and Cancer Stem Cell Modulation in Pancreatic Cancer.
Jiahui LiChristopher BetzlerPhilipp LohneisMarie Christine PoppJiwei QinThomas KalinskiThomas WartmannChristiane J BrunsYue ZhaoFelix C PoppPublished in: International journal of molecular sciences (2020)
(1) Background: IL-17A accelerates pancreatic intraepithelial neoplasia (PanIN) progression. In this study, we examined whether IL-17A/IL-17RA promotes pancreatic ductal adenocarcinoma (PDAC) aggressiveness in terms of survival and cancer stem cell modulation. (2) Methods: In vitro, the wound-healing assay, the sphere formation assay, and flow cytometry were applied to assess cancer stem cell features. In vivo, pancreatic tumors were induced in C57BL/6 mice using electroporation with oncogenic plasmids (P53-/- R172H; KrasG12V). Anti-IL-17 antibodies were administered as immunotherapy. We analyzed IL-17A/IL-17RA related survival using publicly available transcriptomic data (n = 903). (3) Results: IL-17A/IL-17RA expression was not related to survival in PDAC patients. IL-17A neither induces stem cell markers nor increases sphere formation and cell motility in vitro. Blocking the IL-17A/IL-17RA axis in a murine pancreatic cancer model did not improve the survival of mice, but reduced the tumor burden slightly. (4) Conclusions: IL-17A does not promote stem cell expansion in PDAC cell lines. Blocking IL-17A/IL-17RA signaling does not interfere with pancreatic cancer development and progression and may not be considered as a promising monotherapy for PDAC.
Keyphrases
- stem cells
- cancer stem cells
- escherichia coli
- type diabetes
- metabolic syndrome
- single cell
- bone marrow
- mesenchymal stem cells
- cystic fibrosis
- clinical trial
- free survival
- systemic lupus erythematosus
- skeletal muscle
- pseudomonas aeruginosa
- open label
- big data
- interstitial lung disease
- multidrug resistant
- rna seq
- drug induced
- biofilm formation
- idiopathic pulmonary fibrosis