Xu Xiangdong, Wang Bo, Ye Caisheng, Yao Chen, Lin Ying, Huang Xueling, Zhang Yunjian, Wang Shenming
Department of Center of Breast Disease, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou 510080, China.
Cancer Lett. 2008 Mar 18;261(2):147-57. doi: 10.1016/j.canlet.2007.11.028. Epub 2008 Jan 2.
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.
巨噬细胞移动抑制因子（MIF）是肿瘤进展的重要促成因素。不同类型肿瘤中均有MIF过表达的报道。然而，乳腺癌患者中MIF表达与肿瘤病理特征之间的相关性尚未阐明。在本研究中，我们检测了人肿瘤及非肿瘤组织中MIF、血管内皮生长因子（VEGF）和白细胞介素-8（IL-8）的表达。此外，我们研究了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VEGF和IL-8的影响。我们发现，与正常组织相比，乳腺癌组织中MIF过表达。MIF水平与IL-8表达和肿瘤微血管密度（MVD）呈正相关。肿瘤组织中MIF表达阳性的患者与阴性患者相比，无病生存期明显更差。乳腺癌患者血清中MIF水平升高也与血清中IL-8水平升高相关。体外实验成功检测到乳腺癌细胞系中的MIF。然而，正常上皮细胞中其表达水平远低于癌细胞。外源性MIF不会导致内皮管形成和迁移，但会诱导乳腺癌细胞系中VEGF和IL-8分泌呈剂量依赖性增加。总之，我们的研究表明人乳腺癌组织表达MIF。其对VEGF和IL-8的体外作用表明，MIF可能在肿瘤血管生成中发挥作用，从而在乳腺癌发病机制中起重要作用。
