Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug;36(8):e22449.
doi: 10.1096/fj.202101953R.

MIF confers survival advantage to pancreatic CAFs by suppressing interferon pathway-induced p53-dependent apoptosis

Voddu Suresh  1   2 , Pujarini Dash  1 , Sujit Suklabaidya  1 , Krushna Chandra Murmu  2   3 , Prakash K Sasmal  4 , Gajendra M Jogdand  5 , Deepti Parida  1   2 , Manisha Sethi  1   2 , Biswajit Das  1 , Debasish Mohapatra  1   6 , Subha Saha  2   3 , Punit Prasad  3 , Abhay Satoskar  7 , Shantibhusan Senapati  1
Affiliations

MIF confers survival advantage to pancreatic CAFs by suppressing interferon pathway-induced p53-dependent apoptosis

Voddu Suresh et al. FASEB J. 2022 Aug.

Abstract

The presence of activated pancreatic stellate cells (PSCs) in the pancreatic ductal adenocarcinoma (PDAC) microenvironment plays a significant role in cancer progression. Macrophage migration inhibitory factor (MIF) is overexpressed in PDAC tissues and expressed by both cancer and stromal cells. The pathophysiological role of MIF in PDAC-associated fibroblasts or PSCs is yet to be elucidated. Here we report that the PSCs of mouse or cancer-associated fibroblast cells (CAFs) of human expresses MIF and its receptors, whose expression gets upregulated upon LPS or TNF-α stimulation. In vitro functional experiments showed that MIF significantly conferred a survival advantage to CAFs/PSCs upon growth factor deprivation. Genetic or pharmacological inhibition of MIF also corroborated these findings. Further, co-injection of mouse pancreatic cancer cells with PSCs isolated from Mif-/- or Mif+/+ mice confirmed the pro-survival effect of MIF in PSCs and also demonstrated the pro-tumorigenic role of MIF expressed by CAFs in vivo. Differential gene expression analysis and in vitro mechanistic studies indicated that MIF expressed by activated CAFs/PSCs confers a survival advantage to these cells by suppression of interferon pathway induced p53 dependent apoptosis.

Keywords: CAFs; Treg; apCAFs; apoptosis; fibrosis; pancreatic stellate cells; stromal cells.

PubMed Disclaimer

References

REFERENCES

    1. Suklabaidya S, Dash P, Das B, Suresh V, Sasmal PK, Senapati S. Experimental models of pancreatic cancer desmoplasia. Lab Invest. 2018;98:27-40.
    1. Suklabaidya S, Das B, Ali SA, et al. Characterization and use of HapT1-derived homologous tumors as a preclinical model to evaluate therapeutic efficacy of drugs against pancreatic tumor desmoplasia. Oncotarget. 2016;7:41825-41842.
    1. Costa-Silva B, Aiello NM, Ocean AJ, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol. 2015;17:816-826.
    1. Suresh V, Sundaram R, Dash P, et al. Macrophage migration inhibitory factor of Syrian golden hamster shares structural and functional similarity with human counterpart and promotes pancreatic cancer. Sci Rep. 2019;9:15507.
    1. Torres MP, Rachagani S, Souchek JJ, Mallya K, Johansson SL, Batra SK. Novel pancreatic cancer cell lines derived from genetically engineered mouse models of spontaneous pancreatic adenocarcinoma: applications in diagnosis and therapy. PLoS One. 2013;8:e80580.

Publication types

MeSH terms

Substances

LinkOut - more resources