title: Interleukin-8: A potent promoter of human lymphatic endothelial cell growth in gastric cancer.
abstract: Lymphatic metastasis is a major progression route of gastric cancer. Interleukin-8 (IL-8), as an inflammatory cytokine, is induced by Helicobacter pylori infection and is strongly associated with gastric cancer development and metastasis. The blood and lymphatic systems are similar in their function and gene expression profiles. It has been proposed that IL-8 activates angiogenesis. However, the direct role of IL-8 in lymphangiogenesis in gastric cancer remains unclear. We investigated the effect of IL-8 on the growth of human lymphatic endothelial cells (LECs). In addition, protein and mRNA expression of selected lymphangiogenesis markers was assessed in these cells. LECs were co-cultured with gastric cancer SGC7901 cells and exposed to various concentrations of IL-8 (0, 0.2, 0.5, 0.8 and 1.0 ng/ml). The Cell Counting Kit-8 was used to evaluate LEC proliferation (cultured for 1-6 days). Then, protein (immunofluorescence and western blotting) and mRNA [quantitative transcription-polymerase chain reaction (qPCR)] levels were measured in samples obtained from the 24-h cultured cells, for lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1), vascular endothelial growth factor (VEGF)-C, VEGF-D and vascular endothelial growth factor receptor-3 (VEGFR-3). The data presented herein demonstrated that IL-8 promotes the proliferation of LECs and enhances the protein and mRNA expression of LYVE-1. Notably, IL-8 inhibited VEGF-C, VEGF-D and VEGFR-3 protein expression as well as VEGF-D and VEGFR-3 mRNA expression. These findings suggest that IL-8 may be a potent inducer of LECs, although this effect does not appear to involve the VEGF-C/VEGF-D and VEGFR-3 signaling pathway.
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, P.R. China.
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, P.R. China.
authors.forename: Pin-Kang
authors.initials: PK
authors.lastname: Wei
mesh_terms: D049109:Cell Proliferation / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D042583:Lymphangiogenesis / Q000235:genetics; D008207:Lymphatic Metastasis / Q000235:genetics; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis / Q000235:genetics*; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis / Q000235:genetics*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3