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      RANKL/RANK interaction promotes the growth of cervical cancer cells by strengthening the dialogue between cervical cancer cells and regulation of IL-8 secretion.

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          Abstract

          Receptor activator for nuclear factor κB ligand (RANKL) is a member of the tumor necrosis factor (TNF) family. The interaction between RANKL and its receptor RANK plays an important role in the development and function of diverse tissues. However, the expression and role of RANKL in cervical cancer are still unknown. In the present study, we found that RANKL and RANK were highly co-expressed in cervical cancer. HeLa and SiHa cells secreted soluble RANKL (sRANKL), expressed member RANKL (mRANKL) and RANK. Recombinant human RANKL protein had no effect on the viability of HeLa and SiHa cells. Yet, blocking RANKL with an anti-human RANKL neutralizing antibody (α-RANKL) or recombinant human osteoprotegrin (OPG) protein resulted in the downregulation of Ki-67 and B-cell lymphoma 2 (Bcl-2) expression and an increase in Fas and Fas ligand (FasL) expression, as well as a high level of viability and a low level of apoptosis in the HeLa and SiHa cells. In addition, α-RANKL led to a decrease in IL-8 secretion. Recombinant human IL-8 protein reversed the effect of α-RANKL on the expression of proliferation- and apoptosis‑related molecules, and proliferation and apoptosis in the HeLa and SiHa cells. The present study suggests that a high level of mRANKL/RANK expression in cervical cancer lesions plays an important role in the rapid growth of cervical cancer cells possibly through strengthening the dialogue between cervical cancer cells and regulation of IL-8 secretion, which may be a possible target for cervical cancer therapy.

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          Author and article information

          Journal
          Oncol. Rep.
          Oncology reports
          Spandidos Publications
          1791-2431
          1021-335X
          Dec 2015
          : 34
          : 6
          Affiliations
          [1 ] Department of Obstetrics and Gynecology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
          [2 ] Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, P.R. China.
          [3 ] Medical Center of Diagnosis and Treatment for Cervical Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011, P.R. China.
          Article
          10.3892/or.2015.4303
          26398902
          98a7bec3-51a8-4327-b0b1-bab21b2b12fb
          History

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