title: The infiltration and functional regulation of eosinophils induced by TSLP promote the proliferation of cervical cancer cell.
abstract: Cervical cancer is often associated with eosinophil (EOS) infiltration, but the source and the role of EOS are still largely unknown. Our previous work has established that thymic stromal lymphopoietin (TSLP) can stimulate the growth of cervical cancer cell in an autocrine manner. Here, we report that EOS infiltration of the lesion site increased gradually with the progression of cervical cancer. The increase in TSLP secretion in HeLa and SiHa cells induced by hypoxia led to a high level of chemokine CCL17 production by HeLa and SiHa cells, and recruited more EOS to the cancer lesion. In addition, TSLP derived from HeLa and SiHa cells promoted proliferation, up-regulated the levels of anti-inflammatory cytokines (IL-10, IL-4, IL-5 and IL-13), and decreased the expression of CD80 and CD86 of EOS. Such educated EOS significantly promoted proliferation and restricted the apoptosis of cervical cancer cells, which was associated with the up-regulation of Ki-67, PCNA and Bcl-2, and the down-regulation of Fas and FasL in HeLa and SiHa cells. These results suggest that a high level of TSLP in cancer lesions mediated by hypoxia is an important regulator of the progression of cervical cancer by recruiting and licensing tumor-associated EOS to promote the growth of the cervical cancer cell itself. This provides a scientific basis on which potential therapeutic strategies could be targeted to cervical cancer, especially for patients with massive infiltrations of EOS.
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China; Medical Center of Diagnosis and Treatment for Cervical Diseases, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, 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 Medical College, Shanghai 200011, China; Department of Obstetrics and Gynecology, Changzhou No. 2 People's Hospital, Nanjing Medical University, Changzhou 213003, Jiangsu Province, 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 Medical College, Shanghai 200011, 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 Medical College, Shanghai 200011, 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 Medical College, Shanghai 200011, China.
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Meng
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Mei
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, 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 Medical College, Shanghai 200011, China. Electronic address: djli@shmu.edu.cn.
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 Medical College, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China. Electronic address: mqli@fudan.edu.cn.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Li
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008875:Middle Aged; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin
keywords: CCL17; Cervical cancer cells; Eosinophils; Proliferation; TSLP