Macrophage migration inhibitory factor promotes the invasion and metastasis of oral squamous cell carcinoma through matrix metalloprotein-2/9.

Abstract

Macrophage migration inhibitory factor (MIF) has been shown to closely associate with the malignant progression of a variety of human carcinomas. However, the role and its underlying molecular mechanisms of MIF in the invasion and metastasis of oral squamous cell carcinoma (OSCC) still remains unclear. Here, we found that MIF silencing reduced the cell proliferation, migration, and invasion, as well as matrix metalloprotein-2 (MMP-2) and MMP-9 in OSCC cells. Overexpression of MMP-2 or MMP-9 restored the migration and invasion of MIF-knockdown cells, indicating that MMP-2 and MMP-9 are downstream targets of MIF. In the xenograft model, MIF silencing inhibited tumor growth and in lymph metastasis model, MIF silencing reduced tumor metastasis. More importantly, immunohistochemistry staining in a tissue microarray (TMA) demonstrated that MIF expression was positively correlated with clinic stage, recurrence, metastasis, and poor prognosis of patients with OSCC as well as with the levels of MMP-2 or MMP-9 in TMA. Therefore, our findings suggest that MIF may promote the invasion and metastasis of OSCC through the activation of MMP-2 and MMP-9 and prompt further investigation into the therapeutic value of MIF for OSCC treatment.

• Authors: Sha-Sha Wang, Min Zheng, Xin Pang, Mei Zhang, Xiang-Hua Yu, Jing-Biao Wu, Xiao-Lei Gao, Jia-Shun Wu, Xiao Yang, Ya-Jie Tang, Ya-Ling Tang, Xin-Hua Liang
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 58 Issue 10 Pg. 1809-1821 (10 2019) ISSN: 1098-2744 [Electronic] United States
• PMID: 31219646 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Macrophage Migration-Inhibitory Factors
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9
• Intramolecular Oxidoreductases
• MIF protein, human

Topics

• Aged
• Animals
• Carcinoma, Squamous Cell (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Heterografts
• Humans
• Intramolecular Oxidoreductases (genetics)
• Macrophage Migration-Inhibitory Factors (genetics)
• Male
• Matrix Metalloproteinase 2 (genetics)
• Matrix Metalloproteinase 9 (genetics)
• Mice
• Middle Aged
• Mouth Neoplasms (genetics, pathology)
• Neoplasm Invasiveness (genetics, pathology)
• Neoplasm Recurrence, Local (genetics, pathology)
• Neoplasm Staging
• Prognosis