Abstract
Pancreatic cancer is the most lethal digestive cancer and the fourth leading cause of cancer death in the US. IL-39, a heterodimer of p19 and EBI3, is a newly found cytokine and its role in the pathogenesis of neoplasia has not been studied yet. This study was designed to investigate the direct role of IL-39 in the growth of pancreatic cancer. Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the direct effects of IL-39 on cell survival, proliferation and apoptosis of the widely studied pancreatic cancer cell line MiaPaCa-2. We further investigated the possible molecular mechanisms by using RT-PCR and IHC. The percentage of colonies of pancreatic cancer cells increased significantly in the presence of IL-39. This was paralleled with the increase in the OD value of cancer cells in the presence of IL-39. Interestingly, the relative caspase-3 activity in cancer cells decreased significantly in the presence of IL-39. Furthermore, the pro-tumor effect of IL-39 on pancreatic cancer cells correlated with decreased anti-proliferative molecule p21.The anti-apoptotic effect of IL-39 correlated with decreased pro-apoptotic molecule TRAILR1. These results suggest that IL-39 favors growth of pancreatic cancer by promoting growth and inhibiting apoptosis of cancer cells. This suggests that IL-39 acts as a friend to pancreatic cancer. Thus, inhibition of effect of IL-39 on cells might be a promising strategy to treat pancreatic cancer.
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Change history
22 January 2019
The original version of this article unfortunately contained a mistake in the text of the entire article. The word “IL-39” should read as “meteorin-like protein”. This has been corrected with this correction.
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Acknowledgements
This work was supported by the Grant IOER 112-3749 for Yujiang Fang and we thank Mr. Joseph Schmidt, Mr. Nick Caruso, Mr. Benjamin G. Tlapec and Mr.Aldo dominguez for their contributes to this manuscript.
Funding
This study was supported by grants for Yujiang Fang (Iowa Science Foundation Grant ISF 16-8, IOER 05-14-01, IOER 112-3749 and IOER 112-3104).
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Manning, A.A., Zhao, L., Zhu, Z. et al. IL-39 acts as a friend to pancreatic cancer. Med Oncol 36, 12 (2019). https://doi.org/10.1007/s12032-018-1236-y
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DOI: https://doi.org/10.1007/s12032-018-1236-y