Macrophage migration inhibitory factor of Syrian golden hamster shares structural and functional similarity with human counterpart and promotes pancreatic cancer

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that increasingly is being studied in cancers and inflammatory diseases. Though murine models have been instrumental in understanding the functional role of MIF in different pathological conditions, the information obtained from...

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Bibliographic Details
Published in:Scientific reports 2019-10, Vol.9 (1), p.15507-16, Article 15507
Main Authors: Suresh, Voddu, Sundaram, Rajivgandhi, Dash, Pujarini, Sabat, Surendra Chandra, Mohapatra, Debasish, Mohanty, Sneha, Vasudevan, Dileep, Senapati, Shantibhusan
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Angiogenesis
Animal models
Animals
Cell Line, Tumor
Cell Movement
Cell Proliferation - physiology
Crystal structure
Crystallography, X-Ray
Gene Knockdown Techniques
Humans
Inflammatory diseases
Leukocyte migration
Leukocytes (mononuclear)
Leukocytes, Mononuclear - cytology
Macrophage migration inhibitory factor
Macrophage Migration-Inhibitory Factors - chemistry
Macrophage Migration-Inhibitory Factors - genetics
Macrophage Migration-Inhibitory Factors - physiology
Mesocricetus
Mesocricetus auratus
Pancreatic cancer
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Pancreatic Neoplasms - physiopathology
Peripheral blood mononuclear cells
Phylogeny
Protein Conformation
Recombinant Proteins - chemistry
Recombinant Proteins - metabolism
Sequence Homology, Amino Acid
Structure-function relationships
Tumor cells
Vascular Endothelial Growth Factor A - metabolism
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Summary:Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that increasingly is being studied in cancers and inflammatory diseases. Though murine models have been instrumental in understanding the functional role of MIF in different pathological conditions, the information obtained from these models is biased towards a specific species. In experimental science, results obtained from multiple clinically relevant animal models always provide convincing data that might recapitulate in humans. Syrian golden hamster (Mesocricetus auratus), is a clinically relevant animal model for multiple human diseases. Hence, the major objectives of this study were to characterize the structure and function of Mesocricetus auratus MIF (MaMIF) and finally evaluate its effect on pancreatic tumor growth in vivo. Initially, the recombinant MaMIF was cloned, expressed and purified in a bacterial expression system. The MaMIF primary sequence, biochemical properties, and crystal structure analysis showed greater similarity with human MIF. The crystal structure of MaMIF illustrates that it forms a homotrimer as known in human and mouse. However, MaMIF exhibits some minor structural variations when compared to human and mouse MIF. The in vitro functional studies show that MaMIF has tautomerase activity and enhances activation and migration of hamster peripheral blood mononuclear cells (PBMCs). Interestingly, injection of MaMIF into HapT1 pancreatic tumor-bearing hamsters significantly enhanced the tumor growth and tumor-associated angiogenesis. Together, the current study shows a structural and functional similarity between the hamster and human MIF. Moreover, it has demonstrated that a high level of circulating MIF originating from non-tumor cells might also promote pancreatic tumor growth in vivo.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-51947-7