Helicobacter pylori-derived Heat shock protein 60 enhances angiogenesis via a CXCR2-mediated signaling pathway.
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.
Lin
Chen-Si
CS
Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan.
He
Pei-Juin
PJ
Hsu
Wei-Tung
WT
Wu
Ming-Shiang
MS
Wu
Chang-Jer
CJ
Shen
Hsiao-Wei
HW
Hwang
Chia-Hsiang
CH
Lai
Yiu-Kay
YK
Tsai
Nu-Man
NM
Liao
Kuang-Wen
KW
D001426:Bacterial Proteins / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D004730:Endothelium, Vascular / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D023063:Receptors, Interleukin-8B / Q000378:metabolism*
C078096:60K protein, Helicobacter pylori; D001426:Bacterial Proteins; D023063:Receptors, Interleukin-8B