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Macrophage migration inhibitory factor of Syrian golden hamster has similar structure and function as human MIF and promotes pancreatic tumor growth

Pujarini Dash, Rajivgandhi Sundaram, Voddu Suresh, Surendra Chandra Sabat, Debasish Mohapatra, Sneha Mohanty, Dileep Vasudevan, Shantibhusan Senapati
doi: https://doi.org/10.1101/449629
Pujarini Dash
1Tumor Microenvironment and Animal Models Lab, Institute of Life Sciences, Bhubaneswar, Odisha, India
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Rajivgandhi Sundaram
2Macromolecular Crystallography Lab, Institute of Life Sciences, Bhubaneswar, Odisha, India
3Manipal Academy of Higher Education, Manipal, Karnataka, India
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Voddu Suresh
1Tumor Microenvironment and Animal Models Lab, Institute of Life Sciences, Bhubaneswar, Odisha, India
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Surendra Chandra Sabat
4Molecular Biology of Abiotic Stress Lab, Institute of Life Sciences, Bhubaneswar, Odisha, India
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Debasish Mohapatra
1Tumor Microenvironment and Animal Models Lab, Institute of Life Sciences, Bhubaneswar, Odisha, India
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Sneha Mohanty
5Department of Microbiology, Odisha University of Agriculture and Technology, Bhubaneswar, Odisha, India
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Dileep Vasudevan
2Macromolecular Crystallography Lab, Institute of Life Sciences, Bhubaneswar, Odisha, India
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  • For correspondence: senapati@ils.res.in drsantibhusan@yahoo.com dileep@ils.res.in
Shantibhusan Senapati
1Tumor Microenvironment and Animal Models Lab, Institute of Life Sciences, Bhubaneswar, Odisha, India
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  • For correspondence: senapati@ils.res.in drsantibhusan@yahoo.com dileep@ils.res.in
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Abstract

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 structure and function of hamster MIF, and finally evaluate its effect on pancreatic tumor growth in vivo. Initially, the recombinant hamster MIF (rha-MIF) was cloned, expressed and purified in bacterial expression system. The rha-MIF primary sequence, biochemical properties and crystal structure analysis showed a greater similarity with human MIF. The crystal structure of hamster MIF illustrates that it forms a homotrimer as known in human and mouse. However, hamster MIF exhibits some minor structural variations when compared to human and mouse MIF. The in vitro functional studies show that rha-MIF has tautomerase activity and enhances activation and migration of hamster peripheral blood mononuclear cells (PBMCs). Interestingly, injection of rha-MIF 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 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.

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Posted December 19, 2018.
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Macrophage migration inhibitory factor of Syrian golden hamster has similar structure and function as human MIF and promotes pancreatic tumor growth
Pujarini Dash, Rajivgandhi Sundaram, Voddu Suresh, Surendra Chandra Sabat, Debasish Mohapatra, Sneha Mohanty, Dileep Vasudevan, Shantibhusan Senapati
bioRxiv 449629; doi: https://doi.org/10.1101/449629
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Macrophage migration inhibitory factor of Syrian golden hamster has similar structure and function as human MIF and promotes pancreatic tumor growth
Pujarini Dash, Rajivgandhi Sundaram, Voddu Suresh, Surendra Chandra Sabat, Debasish Mohapatra, Sneha Mohanty, Dileep Vasudevan, Shantibhusan Senapati
bioRxiv 449629; doi: https://doi.org/10.1101/449629

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