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BACKGROUND Interleukin-1 alpha (IL-1α) plays an important role in tumorigenesis and angiogenesis of gastric cancer. The interleukin-1 receptor antagonist (IL-1RA) inhibits IL-1 selectively and specifically through IL-1R type I (IL-1RI). However, the underlying mechanism by which IL-1RA modulates the interactions of tumor cells and their micro-environment is poorly understood. We have evaluated the role of IL-1RA in the metastatic process as well as the mutual or reciprocal actions between gastric cancer cells and stromal cells. METHODS The expressions of IL-1α, vascular endothelial growth factor (VEGF), and IL-1RI mRNA were determined by reverse transcriptase-PCR. The regulatory effect of IL-1RA on the secretion of VEGF in human gastric cancer cells and human umbilical vein endothelial cells (HUVECs) was detected by enzyme-linked immunosorbent assay. The effect of IL-1RA on metastatic potential was evaluated using proliferation, invasion, and angiogenesis assays, respectively, including in vitro co-culture system models consisting of tumor cells and stromal cells that were used to detect invasion and angiogenesis. RESULTS Interleukin-1α mRNA was detected in the higher liver metastatic gastric cell line MKN45. IL-1α protein was expressed in MKN45 cells and in HUVECs. VEGF mRNA and protein were detected in the three gastric cancer cell lines (MKN4, NUGC-4, and AGS). Levels of VEGF secreted by gastric cancer cells and HUVECs appeared to be reduced through the action of IL-1RA via IL-1RI in a dose-dependent manner (P < 0.01). IL-1RA significantly inhibited the proliferation and migration of HUVECs (P < 0.01) and tube formation by HUVECs (P < 0.01), both in a dose-dependent manner. Compared with HUVECs grown without cancer cells (control) or with NUGC-4 cells, tube formation by HUVECs was significantly enhanced by co-culture with MKN45 cells (P < 0.01). The enhanced tube formation in the presence of MKN45 cells was inhibited by the addition of IL-1RA (P < 0.01). CONCLUSIONS The IL-1RA downregulated the metastatic potential of gastric cancer through blockage of the IL-1α/VEGF signaling pathways. IL-1RA has the potential to play a role in the treatment of gastric cancer.
Zhenqiang Gong, and
Jiachi Ma, and
He Su, and
Tiankang Guo, and
Hui Cai, and
Quan Chen, and
Xiaodan Zhao, and
Jianbo Qi, and
Jianbo Du
May 1993,
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research,
Zhenqiang Gong, and
Jiachi Ma, and
He Su, and
Tiankang Guo, and
Hui Cai, and
Quan Chen, and
Xiaodan Zhao, and
Jianbo Qi, and
Jianbo Du
August 1991,
The Journal of biological chemistry,
Zhenqiang Gong, and
Jiachi Ma, and
He Su, and
Tiankang Guo, and
Hui Cai, and
Quan Chen, and
Xiaodan Zhao, and
Jianbo Qi, and
Jianbo Du
December 2003,
The Journal of rheumatology,
Zhenqiang Gong, and
Jiachi Ma, and
He Su, and
Tiankang Guo, and
Hui Cai, and
Quan Chen, and
Xiaodan Zhao, and
Jianbo Qi, and
Jianbo Du
September 2006,
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology,
Zhenqiang Gong, and
Jiachi Ma, and
He Su, and
Tiankang Guo, and
Hui Cai, and
Quan Chen, and
Xiaodan Zhao, and
Jianbo Qi, and
Jianbo Du
November 2010,
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition,
Zhenqiang Gong, and
Jiachi Ma, and
He Su, and
Tiankang Guo, and
Hui Cai, and
Quan Chen, and
Xiaodan Zhao, and
Jianbo Qi, and
Jianbo Du
May 2005,
Clinical oncology (Royal College of Radiologists (Great Britain)),
Zhenqiang Gong, and
Jiachi Ma, and
He Su, and
Tiankang Guo, and
Hui Cai, and
Quan Chen, and
Xiaodan Zhao, and
Jianbo Qi, and
Jianbo Du
May 1994,
Annals of the New York Academy of Sciences,
Zhenqiang Gong, and
Jiachi Ma, and
He Su, and
Tiankang Guo, and
Hui Cai, and
Quan Chen, and
Xiaodan Zhao, and
Jianbo Qi, and
Jianbo Du
January 2000,
Cancer investigation,
Zhenqiang Gong, and
Jiachi Ma, and
He Su, and
Tiankang Guo, and
Hui Cai, and
Quan Chen, and
Xiaodan Zhao, and
Jianbo Qi, and
Jianbo Du
January 1996,
Anticancer research,
Zhenqiang Gong, and
Jiachi Ma, and
He Su, and
Tiankang Guo, and
Hui Cai, and
Quan Chen, and
Xiaodan Zhao, and
Jianbo Qi, and
Jianbo Du
May 2008,
Digestive diseases and sciences,
