Macrophage migration inhibitory factor enhances neoplastic cell invasion by inducing the expression of matrix metalloproteinase 9 and interleukin-8 in nasopharyngeal carcinoma cell lines

• Published in: Chinese medical journal Vol. 117; no. 1; pp. 107 - 114
• Main Author: 李智 任艺 吴琦嫦 林素暇 梁英杰 梁惠珍
• Format: Journal Article
• Language: English
• Published: China Department of Pathology, Sun Yat-sen Medical College, Sun Yat-sen University, Guangzhou 510089, China%Department of Surgery, Hong Kong University, Hong Kong, China %Department of Obstetrics and Gynecology, Guangzhou Maternity and Infant Hospital, Guangzhou 510180, China 2004
• Subjects: Blotting, Western; Cell Line, Tumor; Electrophoresis, Polyacrylamide Gel; Humans; Interleukin-8 - analysis; Macrophage Migration-Inhibitory Factors - pharmacology; Matrix Metalloproteinase 2 - analysis; Matrix Metalloproteinase 9 - analysis; Nasopharyngeal Neoplasms - pathology; Neoplasm Invasiveness - physiopathology; Reverse Transcriptase Polymerase Chain Reaction; 基质金属蛋白酶9; 巨噬细胞转移抑制因子; 白细胞介素8; 肿瘤侵袭; 鼻咽癌; migration inhibitory factor; neoplasm; invasion; interleukin-8; matrix metalloproteinases; nasopharyngeal
• ISSN: 0366-6999; 2542-5641

Background Nasopharyngeal carcinoma (NPC) shows highly invasive and metastatic features. This study aims to investigate macrophage migration inhibitory factor (MIF)-induced invasion of NPC cells in vitro and the effects on matrix metalloproteinases (MMPs) and interleukin-8 (IL-8), and to study the mechanism of tumor cell invasion and metastasis in the early stage of NPC.Methods Two nasopharyngeal carcinoma cell lines, CNE-1 and CNE-2, were adopted in this study.The NPC cell invasion and migration were evaluated by microinvasion assay. The variation of expression percentages of MMP2- or MMP9-positive cells was detected by flow cytometry in two cell lines with or without MIF treatment. Western blotting and RT-PCR were used to assay the protein and mRNA expressions of MMP2 and MMP9. The IL-8 concentration secreted by NPC cells was compared with the cells with different treatments using ELISA.Results After treating with MIF for 48 hours, the cell numbers of CNE-1 and CNE-2 which went through the 8-μm filter membrane were increased. Compared with non-MIF treated NPC cells,significant difference could be found both in CNE-1 (P=0.005) and CNE-2 cells (P=0.001) . The percentages of MMP9-positive cells were significantly increased in both CNE-1 [from (28.5±2.5)% to (82.4±3.5)%, P=0.001] and CNE-2 [from (32.8 ±3.5)% to (86. 1±1.6)%, P=0.002].The relative intensity of MMP9 protein expression was also enhanced in both cell lines (CNE-1:from 83.1±6.0 to 242.9±22.9, P=0.002; CNE-2: from 84.4±4.3 to 278.9±29.7, P=0.003).Correspondingly, the increased MMP9 mRNA expression level was significantly detectable in both cell lines. The concentration of IL-8 in the supernatant of CNE-2 was higher [(1201.8±593.3)pg/ml] after treatment. It was also remarkably higher than that in the supernatant of CNE-2 without treatment (P=0.026). However, there was no significant difference in the concentration variation of IL-8 in CNE-1 (P=0.581), while the IL-8 mRNA level was only enhanced in CNE-2.Conclusions MIF can induce potent invasion of NPC cell lines in vitro, and the infiltrating lymphocytes in NPC might be responsible for theinvasion and metastasis of tumor cells. MIF cytokine which is secreted by these infiltrating lymphocytes might contribute to the invasion aswell as metastasis of NPC in the early stages by induction of MMP9 and IL-8 in an indirectpathway.