title: Chemokine CCL17 induced by hypoxia promotes the proliferation of cervical cancer cell.
abstract: Cervical cancer is often associated with hypoxia and many kinds of chemokines. But the relationship and role of hypoxia and Chemokine (C-C motif) ligand 17 (CCL17) in cervical cancer are still unknown. Here, we found that CCL17 was high expressed in cervical cancer. HeLa and SiHa cells could secrete CCL17 in a time-dependent manner. Hypoxia increased expression of CCL17 receptor (CCR4) on HeLa and SiHa cells. Treatment with recombination human CCL17 (rhCCL17) led to an elevation of cell proliferation in HeLa and SiHa cells in a dose-dependent manner. In contrast, blocking CCL17 with anti-human CCL17 neutralizing antibody (α-CCL17) played an oppose effect. However, rhCCL17 had no effect on apoptosis in cervical cancer cells. Further analysis showed that hypoxia promoted the proliferation of HeLa and SiHa cells, and these effects could be reversed by α-CCL17. Stimulation with the inhibitor for c-Jun N-terminal kinase (JNK) or signal transducers and activator of transcription 5 (STAT5) signal pathway not only directly decreased the proliferation of HeLa and SiHa cells, but also abrogated the stimulatory effect of rhCCL17 on the proliferation of HeLa and SiHa cells. These results suggest that a high level of CCL17 in cervical cancer lesions is an important regulator in the proliferation of cervical cancer cells through JNK and STAT5 signaling pathways. In this process, hypoxia magnifies this effect by up-regulating CCR4 expression and strengthening the interaction of CCL17/CCR4.
authors.affiliation: Department of Obstetrics and Gynecology, Changzhou NO.2 People's Hospital, Nanjing Medical University Changzhou 213003, Jiangsu Province, The People's Republic of China ; Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China.
authors.forename: Li-Bing
authors.initials: LB
authors.lastname: Liu
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China ; Medical Center of Diagnosis and Treatment for Cervical Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China.
authors.forename: Kai-Kai
authors.initials: KK
authors.lastname: Chang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China.
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Shang
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Meng
authors.affiliation: Department of Obstetrics and Gynecology, Changzhou NO.2 People's Hospital, Nanjing Medical University Changzhou 213003, Jiangsu Province, The People's Republic of China ; Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China.
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Yerkes National Primate Research Center, Emory University Atlanta, GA 30329, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China.
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Yuan
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011, The People's Republic of China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jin
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China.
authors.forename: Da-Jin
authors.initials: DJ
authors.lastname: Li
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai 200011, The People's Republic of China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011, The People's Republic of China.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
keywords: CCL17; cervical cancer cells; hypoxia; proliferation