Abstract
Purpose
While macrophage migration inhibitory factor (MIF) has been extensively studied in the context of inflammation and inflammatory disorders, less work has been devoted to its involvement in cancer, notably in neoplastic progression. In a previous study, we have found evidence that MIF plays a role in head and neck squamous cell carcinomas (HNSCC). The current investigations were undertaken in order to estimate the importance of the MIF receptor, CD74 in the progression of HNSCC.
Methods and results
In a cohort of 46 cases of oral cavity carcinomas, immunohistochemical staining revealed an increase in CD74 expression during progression from benign lesions to carcinoma. As shown by cell culture experiments using squamous carcinoma cell line (SCCVII) transduced with anti-CD74 shRNA, the amount of cell-produced VEGF was lower in SCCVII CD74KD cell line compared with control SCCVII CD74sc cell line, suggesting that CD74 could be implicated in angiogenesis in vivo. Furthermore, knockdown of CD74 decreased proliferation of SCCVII cells in vitro. The migration of SCCVII cells, as well as the cell secretion of matrix metallopeptidase 9, was also negatively affected by CD74 knockdown. These observations in vitro were confirmed in an orthotopic mouse model of SCC where tumors produced by SCCVII CD74KD cell inoculation were found to grow more slowly than tumors generated by SCCVII CD74sc cells.
Conclusion
The clinical observations and experimental data reported here suggest that CD74, as well as MIF, plays a pivotal role in HNSCC progression.







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Acknowledgments
NK is the recipient of a fellowship from the “Fondation Rose and Jean Hoguet” and of a grant (“Televie”) from the National Fund for Scientific Research. GL is Senior Research Associate of the National Fund for Scientific Research (Belgium).
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The authors declare no conflict of interest.
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Guy Laurent and Sven Saussez have contributed equally to this work and should be regarded as joint last authors.
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Kindt, N., Lechien, J.R., Nonclercq, D. et al. Involvement of CD74 in head and neck squamous cell carcinomas. J Cancer Res Clin Oncol 140, 937–947 (2014). https://doi.org/10.1007/s00432-014-1648-9
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DOI: https://doi.org/10.1007/s00432-014-1648-9