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Macrophage migration inhibitory factor of Syrian golden hamster shares structural and functional similarity with human counterpart and promotes pancreatic cancer
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Macrophage migration inhibitory factor of Syrian golden hamster shares structural and functional similarity with human counterpart and promotes pancreatic cancer
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Journal Article
Macrophage migration inhibitory factor of Syrian golden hamster shares structural and functional similarity with human counterpart and promotes pancreatic cancer
2019
Overview
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
.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 64/60
/ 82/51
/ 82/80
/ 96/106
/ Animals
/ Cell Proliferation - physiology
/ Humanities and Social Sciences
/ Humans
/ Leukocytes, Mononuclear - cytology
/ Macrophage migration inhibitory factor
/ Macrophage Migration-Inhibitory Factors - chemistry
/ Macrophage Migration-Inhibitory Factors - genetics
/ Macrophage Migration-Inhibitory Factors - physiology
/ Pancreatic Neoplasms - metabolism
/ Pancreatic Neoplasms - pathology
/ Pancreatic Neoplasms - physiopathology
/ Peripheral blood mononuclear cells
/ Recombinant Proteins - chemistry
/ Recombinant Proteins - metabolism
/ Science
/ Sequence Homology, Amino Acid
/ Structure-function relationships
/ Tumors
