Chronic macrophage migration inhibitory factor exposure induces mesenchymal epithelial transition and promotes gastric and colon cancers

Katherine T. Morris, Robert A. Nofchissey, Iryna Pinchuk, Ellen J. Beswick

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Macrophage Migration Inhibitory Factor (MIF) is an inflammatory cytokine that is highly produced in gastrointestinal cancers. Since chronic inflammation is a risk factor for tumorigenesis in these cancers, in this study, the role of MIF in protumorigenic events was examined. MIF and its receptor, CD74, were examined in gastric and colon tumors and found to be increased in most tumors with significantly higher expression in tumors from patients with lymph node metastasis. MIF was also found to be highly produced by cancer associated fibroblasts isolated from human tumors compared to fibroblasts from matched normal tissues from uninvolved areas. Fibroblast-produced MIF highly increased GI cancer cell proliferation, which was decreased upon neutralizing MIF or CD74. Chronic MIF treatment led to sustained proliferation and signaling events in non-transformed GI fibroblast cells, which was maintained upon removing MIF treatment for 8 weeks. Additionally, chronic treatment of normal GI cells expressing fibroblast markers for up to 16 weeks with MIF led to a drastic decrease of fibroblast markers with concurrent increase of epithelial markers. Transformation was examined by telomerase and focus forming assays. These results suggest the MIF promotes mesenchymal epithelial transition, cell transformation and tumorigenesis in GI cancers, and thus may be an important link between chronic inflammation and tumorigenesis.

Original languageEnglish (US)
Article numbere98656
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 2 2014

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Macrophage Migration-Inhibitory Factors
Epithelial-Mesenchymal Transition
stomach neoplasms
Fibroblasts
colorectal neoplasms
Colonic Neoplasms
Stomach Neoplasms
fibroblasts
Tumors
neoplasms
Neoplasms
carcinogenesis
Carcinogenesis
Cells
Telomerase
Cell proliferation
inflammation
Inflammation
telomerase
Gastrointestinal Neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Chronic macrophage migration inhibitory factor exposure induces mesenchymal epithelial transition and promotes gastric and colon cancers. / Morris, Katherine T.; Nofchissey, Robert A.; Pinchuk, Iryna; Beswick, Ellen J.

In: PLoS One, Vol. 9, No. 6, e98656, 02.06.2014.

Research output: Contribution to journalArticle

Morris, Katherine T. ; Nofchissey, Robert A. ; Pinchuk, Iryna ; Beswick, Ellen J. / Chronic macrophage migration inhibitory factor exposure induces mesenchymal epithelial transition and promotes gastric and colon cancers. In: PLoS One. 2014 ; Vol. 9, No. 6.
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