Activation of Integrin β1 Mediates the Increased Malignant Potential of Ovarian Cancer Cells Exerted by Inflammatory Cytokines

Author(s): Zongyuan Yang, Xiaoshui Zhou, Yi Liu, Cheng Gong, Xiao Wei, Taoran Zhang, Ding Ma, Qinglei Gao.

Journal Name:Anti-Cancer Agents in Medicinal Chemistry

Volume 14 , Issue 7 , 2014

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.

Keywords: EMT, Inflammatory cytokines, ITGB1, Metastasis, MMP2.

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Article Details

VOLUME: 14
ISSUE: 7
Year: 2014
Page: [955 - 962]
Pages: 8
DOI: 10.2174/1871520614666140613123108
Price: $58