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Helicobacter pylori-derived Heat shock protein 60 enhances angiogenesis via a CXCR2-mediated signaling pathway |
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| Authors: | Chen-Si Lin Pei-Juin He Ming-Shiang Wu Hsiao-Wei Shen Yiu-Kay Lai Kuang-Wen Liao |
| Affiliation: | a Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan b School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan c Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan d Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan e Institute of Molecular Medicine and Bioengineering, National Chiao-Tung University, Hsin-Chu, Taiwan f Department of Life Science, Institute of Biotechnology, National Tsing Hua University, Hsin-Chu, Taiwan g Yung-Shin Pharmaceutical Industry Co., Ltd., Tachia, Taichung, Taiwan h School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan |
| Abstract: | Helicobacter pylori is a potent carcinogen associated with gastric cancer malignancy. Recently, H. pylori Heat shock protein 60 (HpHSP60) has been reported to promote cancer development by inducing chronic inflammation and promoting tumor cell migration. This study demonstrates a role for HpHSP60 in angiogenesis, a necessary precursor to tumor growth. We showed that HpHSP60 enhanced cell migration and tube formation, but not cell proliferation, in human umbilical vein endothelial cells (HUVECs). HpHSP60 also indirectly promoted HUVEC proliferation when HUVECs were co-cultured with supernatants collected from HpHSP60-treated AGS or THP-1 cells. The angiogenic array showed that HpHSP60 dramatically induced THP-1 cells and HUVECs to produce the chemotactic factors IL-8 and GRO. Inhibition of CXCR2, the receptor for IL-8 and GRO, or downstream PLCβ2/Ca2+-mediated signaling, significantly abolished HpHSP60-induced tube formation. In contrast, suppression of MAP K or PI3 K signaling did not affect HpHSP60-mediated tubulogenesis. These data suggest that HpHSP60 enhances angiogenesis via CXCR2/PLCβ2/Ca2+ signal transduction in endothelial cells. |
| Keywords: | Helicobacter pylori Heat shock protein 60 Angiogenesis CXCR2 |
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