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.
J Cancer Res Clin Oncol. 2013 Feb;139(2):287-95. doi: 10.1007/s00432-012-1330-z. Epub 2012 Oct 12.
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.
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.
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.
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.
腺样囊性癌（ACC）是一种常见于唾液腺的恶性肿瘤，由于局部复发和远处转移率高，其长期预后较差。巨噬细胞移动抑制因子（MIF）是一种多功能细胞因子，最近已成为各种癌症中的促肿瘤因子。本研究旨在探讨 MIF 在 ACC 中的表达状态和功能意义。
通过免疫组织化学染色评估 MIF、HIF-1α、MMP-9、p53 和 p-JNK 在 ACC 组织中的表达水平。在体外，ACC-2 细胞用重组人 MIF（rMIF）或 ISO-1（MIF 的抑制剂）在不同浓度和时间下孵育，然后检测细胞生长、活力、迁移和侵袭以及几种细胞信号的表达水平。
免疫组化结果表明 MIF 在 ACC 组织中过度表达，并且与远处转移有关。进一步分析表明，MIF 染色与 p-JNK 之间存在显著相关性。此外，体外研究表明，用 ISO-1 处理 ACC 细胞可显著减弱细胞迁移和侵袭能力，而 rMIF 的促进作用有限。更重要的是，MIF 抑制可导致 JNK 激活，与 ACC 组织的免疫组化发现相关。
研究结果表明，MIF 可能是 ACC 发病机制中的重要因素，可能促进癌症转移，这可能涉及 JNK 失活。进一步研究 MIF 介导的分子事件可能为 ACC 的治疗提供新的见解。
