title: RANKL/RANK interaction promotes the growth of cervical cancer cells by strengthening the dialogue between cervical cancer cells and regulation of IL-8 secretion.
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.
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Shang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, P.R. China.
authors.forename: Li-Bing
authors.initials: LB
authors.lastname: Liu
authors.affiliation: Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, P.R. China.
authors.forename: Kai-Kai
authors.initials: KK
authors.lastname: Chang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, P.R. China.
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: Medical Center of Diagnosis and Treatment for Cervical Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.affiliation: Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, P.R. China.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Jin-Jin
authors.initials: JJ
authors.lastname: Yu
mesh_terms: D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D053222:Fas Ligand Protein / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D053244:Osteoprotegerin / Q000008:administration & dosage; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000096:biosynthesis / Q000235:genetics*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D057134:Antibodies, Neutralizing; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016209:Interleukin-8; D053244:Osteoprotegerin; D019253:Proto-Oncogene Proteins c-bcl-2; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011994:Recombinant Proteins; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human