title: Interleukin-8 secretion by ovarian cancer cells increases anchorage-independent growth, proliferation, angiogenic potential, adhesion and invasion.
abstract: It has been shown that IL-8 is elevated in ovarian cyst fluid, ascites, serum, and tumor tissue from ovarian cancer (OVCA) patients, and increased IL-8 expression correlates with poor prognosis and survival. However, the exact role that IL-8 plays in this malignancy or whether IL-8 can regulate malignant behavior has not been established. Here we demonstrate that overexpression of IL-8 in non-IL-8-expressing A2780 cells (by transfecting with plasmid encoding for sense IL-8) increases anchorage-independent growth, proliferation, angiogenic potential, adhesion and invasion while depletion of endogenous IL-8 expression in IL-8-overexpressing SKOV-3 cells (by transfecting with plasmid encoding for antisense IL-8) decreases the above effects. Further investigation indicates that IL-8-stimulated cell proliferation correlates with alteration of cell cycle distribution by increasing levels of cell cycle-regulated Cyclin D1 and Cyclin B1 proteins as well as activation of PI3K/Akt and Raf/MEK/ERK, whereas IL-8-enhanced OVCA cell invasive correlates with increased MMP-2 and MMP-9 activity and expression. Our data suggest that IL-8 secreted by OVCA cells promotes malignant behavior of these cells via inducing intracellular molecular signaling. Therefore, modulation of IL-8 expression or its related signaling pathway may be a promising strategy for controlling the progression and metastasis of OVCA.
authors.affiliation: TianJin Key Laboratory for Biomarkers of Occupational and Environmental Hazard, Tianjin, People's Republic of China. wy68wy68@yahoo.com.cn
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Rui Cheng
authors.initials: RC
authors.lastname: Xu
authors.forename: Xiao Lei
authors.initials: XL
authors.lastname: Zhang
authors.forename: Xiu Long
authors.initials: XL
authors.lastname: Niu
authors.forename: Ye
authors.initials: Y
authors.lastname: Qu
authors.forename: Ling Zhi
authors.initials: LZ
authors.lastname: Li
authors.forename: Xiang Yan
authors.initials: XY
authors.lastname: Meng
mesh_terms: D002448:Cell Adhesion; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C534699:CCNB1 protein, human; C530104:CCND1 protein, human; C508606:CXCL8 protein, human; D056744:Cyclin B1; D016209:Interleukin-8; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9