Overexpression of macrophage migration inhibitory factor induces angiogenesis in human breast cancer
Overexpression of macrophage migration inhibitory factor induces angiogenesis in human breast cancer
复制标题
巨噬细胞迁移抑制因子的过度表达诱导人乳腺癌血管生成
DOI：
10.1016/j.canlet.2007.11.028
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发表时间：
2008-03-18
期刊：
影响因子：
9.7
通讯作者：
Wang, Shenming
中科院分区：
文献类型：
--
作者：
Xu, Xiangdong;Wang, Bo;Wang, Shenming
巨噬细胞移动抑制因子(MIF)被认为是肿瘤进展的重要因素。MIF在不同类型的肿瘤中均有过表达的报道。然而，MIF在乳腺癌中的表达与肿瘤病理特征之间的关系尚不清楚。在本研究中，我们检测了MIF、血管内皮生长因子(VEGF)和白介素8(IL-8)在有无肿瘤组织中的表达。此外，我们还研究了MIF在MDA-MB-231、MCF-7(乳腺癌细胞系)和MCF-10A(上皮细胞系)细胞中的表达及其对血管内皮生长因子和IL-8的影响。我们发现MIF在乳腺癌组织中的表达高于正常组织。MIF水平与肿瘤微血管密度(MVD)呈正相关。肿瘤组织中MIF表达阳性患者的无瘤生存率明显低于MIF表达阴性患者。研究还发现，乳腺癌患者血清中MIF水平的升高与IL-8水平的升高有关。体外实验成功地检测到乳腺细胞系中的MIF。而在正常上皮细胞中，其表达水平明显低于癌细胞。外源性MIF不能引起内皮管的形成和迁移，但可诱导乳腺癌细胞株中血管内皮生长因子和IL-8的分泌呈剂量依赖性增加。综上所述，我们的研究表明人类乳腺癌组织表达MIF。其对血管内皮生长因子和IL-8的体外作用表明，MIF可能有助于肿瘤的血管生成，从而在乳腺癌的发病机制中发挥重要作用，(C)2007爱思唯尔爱尔兰有限公司。保留所有权利。
Macrophage migration inhibitory factor (MIF) is known to be an important contributor to tumor progression. Overexpression of MIF has been reported in different types of tumors. However, the correlation between MIF expression and tumor pathologic features in patients with breast cancer has not been elucidated. In this study, we examined the expression of MIF, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in human tissues with or without tumor. In addition, we investigated the expression of MIF in MDA-MB-231, MCF-7 (breast cancer cell lines) and MCF-10A (epithelial cell line) cells, and its effect on VEGF and IL-8. We found that MIF was overexpressed in breast cancer tissues compared with normal ones. The level of MIF showed the positive correlation between the expression of IL-8 and tumor microvessel density (MVD). The patients with positive MIF expression in tumor tissues showed a significantly worse disease-free survival compared with negative ones. Increased MIF serum levels were also found to correlate with higher levels of IL-8 in the sera of the patients with breast cancer. In vitro experiments successfully detected MIF in breast cell lines. However, the expression level of it by normal epithelial cells was much less than that of cancer cells. Exogenous MIF did not cause endothelial tube formation and migration but induced a dose dependent increase in VEGF and IL-8 secretion in breast cancer cell lines. In summary, our studies show that human breast cancer tissue expresses MIF. Its in vitro effect on VEGF and IL-8 indicates that MIF may contribute to tumor in angiogenesis and thus play an important role in the pathogenesis of breast cancer, (C) 2007 Elsevier Ireland Ltd. All rights reserved.