Overexpression of macrophage migration inhibitory factor in adenoid cystic carcinoma: correlation with enhanced metastatic potential.
OBJECTIVE
Adenoid cystic carcinoma (ACC) is a malignant tumor frequently arising in salivary glands with poor long-term prognosis due to high rates of local recurrences and distant metastases. Macrophage migration inhibitory factor (MIF) is a multi-functional cytokine and has recently emerged as a pro-tumorigenic factor in various cancers. This study is designed to investigate the expression status and functional significance of MIF in ACC.


METHODS
Immunohistochemical staining was performed to evaluate the expression levels of MIF, HIF-1α, MMP-9, p53, and p-JNK in ACC tissues. In vitro, ACC-2 cells were exposed to recombinant human MIF (rMIF) or ISO-1 (an inhibitor of MIF) at different concentrations and times, followed by the detection of cell growth, viability, migration, and invasion, as well as the expression levels of several cellular signals.


RESULTS
The immunohistochemical results demonstrated the overexpression of MIF in ACC tissues as well as its association with the distant metastasis. Further analyses showed a significant correlation between the staining of MIF and p-JNK. Moreover, the in vitro studies revealed that the treatment for ACC cells with ISO-1 significantly attenuated cell migratory and invasive capacity, as opposed to the limited promotive effects of rMIF. More importantly, MIF inhibition could cause the activation of JNK, correlating with the immunohistochemical findings on ACC tissues.


CONCLUSIONS
The results suggest that MIF is likely to be an important player in the pathogenesis of ACC and may promote cancer metastasis, which possibly involves JNK inactivation. Further investigation of MIF-mediated molecular events may provide novel insights into the treatment for ACC.
The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
Hui
H
Liu
Gang
G
Chen
Wei
W
Zhang
Jun-Yi
JY
Zhu
Zhao-Quan
ZQ
Lin
Zhong-Cheng
ZC
Gong
Feng-Qin
FQ
Wang
Jun
J
Jia
Zhi-Jun
ZJ
Sun
Yi-Fang
YF
Zhao
D003528:Carcinoma, Adenoid Cystic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
C462499:3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester; D007555:Isoxazoles; D008263:Macrophage Migration-Inhibitory Factors; D048670:MAP Kinase Kinase 4