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Macrophage migration inhibitory factor promotes the invasion and metastasis of oral squamous cell carcinoma through matrix metalloprotein‐2/9
Author(s) -
Wang ShaSha,
Zheng Min,
Pang Xin,
Zhang Mei,
Yu XiangHua,
Wu JingBiao,
Gao XiaoLei,
Wu JiaShun,
Yang Xiao,
Tang YaJie,
Tang YaLing,
Liang XinHua
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23067
Subject(s) - macrophage migration inhibitory factor , metastasis , cancer research , biology , matrix metalloproteinase , gene silencing , gene knockdown , cell migration , immunohistochemistry , cell , cancer , pathology , immunology , cell culture , medicine , cytokine , biochemistry , genetics , gene
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.