Role of MIF/CXCL8/CXCR2 signaling in the growth of nasopharyngeal carcinoma tumor spheres.

Abstract

Macrophage migration inhibitory factor (MIF) and CXCL8 (also named IL-8) are strongly expressed in the tissues of nasopharyngeal carcinoma (NPC). However, their role in the growth of NPC has not been fully examined. This study aims to evaluate the functions of MIF and CXCL8 on the growth of NPC tumor spheres. The elevated expression of CXCL8 in tumor over normal tissues was confirmed in 37 pairs of biopsies from NPC patients. In the in vitro study, all the poorly differentiated NPC cell lines, including the EBV-positive C666-1, and the EBV-negative CNE-1, CNE-2, SUNE-1, HNE-1 and HONE-1 cells, were found to express CXCL8 and MIF. Therefore, the EBV-positive C666-1 cell was selected to examine for the role of MIF and CXCL8 in the growth of the NPC tumor spheres. Functional study showed that the growth of C666-1 tumor spheres, under the nutrient poor or growth factor supplemented culture conditions, could be inhibited by the CXCL8 specific peptide inhibitor. The growth of the tumor spheres could also be reduced by the CXCR2 specific inhibitor SB225002 or the PI3K/AKT inhibitor LY294002, indicating that the endogenously produced CXCL8 plays an autocrine role in the growth of the tumor spheres. Further mechanistic studies revealed that the gene expression of CXCL8 could be reduced by the MIF specific small interfering RNA (siRNA) or NF-κB inhibitor parthenolide, and the growth of tumor spheres was also reduced after MIF siRNA transfection. Taken together, the present study highlights the role of MIF/CXCL8/CXCR2 axis in the growth of NPC tumor spheres. Chemotherapeutic interference of this signaling pathway may help to control the growth of the NPC tumor.

• Authors: Ming-Chu Lo, Tak-Chun Yip, Kai-Cheong Ngan, Wai-Wai Cheng, Chun-Key Law, Pui-Shan Chan, King-Chi Chan, Chris Kong-Chu Wong, Ricky Ngok-Shun Wong, Kwok-Wai Lo, Wai-Tong Ng, Wing-Mui Lee, Sai-Wah Tsao, Lai-Wan Kwong, Maria Li Lung, Nai-Ki Mak
• Journal: Cancer letters (Cancer Lett) Vol. 335 Issue 1 Pg. 81-92 (Jul 10 2013) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 23403077 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• CXCL8 protein, human
• Chromones
• Interleukin-8
• Macrophage Migration-Inhibitory Factors
• Morpholines
• NF-kappa B
• Phenylurea Compounds
• Phosphoinositide-3 Kinase Inhibitors
• RNA, Small Interfering
• Receptors, Interleukin-8B
• SB 225002
• Snail Family Transcription Factors
• Transcription Factors
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Intramolecular Oxidoreductases
• MIF protein, human

Topics

• Carcinoma (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Chromones (pharmacology)
• Gene Expression
• Gene Knockdown Techniques
• Humans
• Interleukin-8 (antagonists & inhibitors, genetics, metabolism)
• Intramolecular Oxidoreductases (genetics, metabolism)
• Macrophage Migration-Inhibitory Factors (genetics, metabolism)
• Morpholines (pharmacology)
• NF-kappa B (genetics, metabolism)
• Nasopharyngeal Neoplasms (metabolism, pathology)
• Phenylurea Compounds (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• RNA, Small Interfering (genetics)
• Receptors, Interleukin-8B (antagonists & inhibitors, genetics, metabolism)
• Signal Transduction
• Snail Family Transcription Factors
• Spheroids, Cellular (metabolism, pathology)
• Transcription Factors (genetics, metabolism)