title: Activation of integrin β1 mediates the increased malignant potential of ovarian cancer cells exerted by inflammatory cytokines.
abstract: Epithelial ovarian cancer (EOC) is a highly lethal gynecological malignancy since it could not be discovered until at late stage. Identifying the molecular phenotype alteration during the development and progression of ovarian cancer is an urgent demand for the targeted intervention therapy. Recently, inflammation and Integrin beta 1(ITGB1), a subunit of heterodimeric transmembrane receptors family, had been pointed out to be involved in promoting ovarian tumorigenesis and cancer progression, respectively. However, the relationship between ITGB1 and the inflammatory mediators in ovarian cancer progression remains obscure. In the present study, ITGB1 was observed to be frequently upregulated in ovarian cancer, overexpression of ITGB1 led to a more invasive and mesenchymal phenotype. Furthermore, our results also provided evidence concerning the role of inflammatory cytokines (IL-6, TGF-β1 and SDF-1) in ITGB1 expression as well as in the malignant potential of ovarian cancer cells. Consistently, sh-RNA mediated knocking down of ITGB1 evidently reduced tumor growth and peritoneal dissemination in in vivo Nod-scid SKOV3 orthotopic xenograft mice. Overall, the present data suggested that ITGB1 upregulation was involved in the regulation of tumorigenesis and disease exacerbation exerted by inflammatory cytokines as IL-6, TGF-β1 and SDF-1, and suggested that targeting ITGB1 and the underlying inflammatory modulator was an attractive strategy for therapeutic intervention during ovarian carcinogenesis.
authors.forename: Zongyuan
authors.initials: Z
authors.lastname: Yang
authors.forename: Xiaoshui
authors.initials: X
authors.lastname: Zhou
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Cheng
authors.initials: C
authors.lastname: Gong
authors.forename: Xiao
authors.initials: X
authors.lastname: Wei
authors.forename: Taoran
authors.initials: T
authors.lastname: Zhang
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv. Wuhan, Hubei 430030, China. qlgao@tjh.tjmu.edu.cn.
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D064593:Heterografts; D006801:Humans; D007249:Inflammation / Q000276:immunology; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000473:pathology; D009368:Neoplasm Transplantation; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010529:Peritoneal Cavity / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D059016:Tumor Microenvironment; D015854:Up-Regulation
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019012:Integrin beta1; D015850:Interleukin-6; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1