Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan.
Biochem Biophys Res Commun. 2010 Jun 25;397(2):283-9. doi: 10.1016/j.bbrc.2010.05.101. Epub 2010 May 24.
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 PLCbeta2/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/PLCbeta2/Ca2+ signal transduction in endothelial cells.
幽门螺杆菌是一种与胃癌恶性肿瘤相关的强效致癌剂。最近，研究报道幽门螺杆菌热休克蛋白 60（HpHSP60）通过诱导慢性炎症和促进肿瘤细胞迁移来促进癌症发展。本研究表明 HpHSP60 在血管生成中起作用，血管生成是肿瘤生长的必要前提。我们发现 HpHSP60 增强了人脐静脉内皮细胞（HUVEC）的细胞迁移和管形成，但不促进细胞增殖。当将 HpHSP60 处理的 AGS 或 THP-1 细胞的上清液与 HUVEC 共培养时，HpHSP60 还间接促进了 HUVEC 的增殖。血管生成阵列显示，HpHSP60 显著诱导 THP-1 细胞和 HUVEC 产生趋化因子 IL-8 和 GRO。抑制 CXCR2，即 IL-8 和 GRO 的受体，或下游 PLCβ2/Ca2+介导的信号转导，可显著阻断 HpHSP60 诱导的管形成。相比之下，抑制 MAP K 或 PI3 K 信号转导不会影响 HpHSP60 介导的管形成。这些数据表明，HpHSP60 通过内皮细胞中的 CXCR2/PLCβ2/Ca2+信号转导增强血管生成。
