Title:Activation of Integrin β1 Mediates the Increased Malignant Potential of Ovarian Cancer Cells Exerted by Inflammatory Cytokines
Volume: 14
Issue: 7
Author(s): Zongyuan Yang, Xiaoshui Zhou, Yi Liu, Cheng Gong, Xiao Wei, Taoran Zhang, Ding Ma and Qinglei Gao
Affiliation:
Keywords:
EMT, Inflammatory cytokines, ITGB1, Metastasis, MMP2.
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.
