Cervical cancer cell–derived angiopoietins promote tumor progression

Metastatic or recurrent cervical cancer has limited treatment options and a high rate of mortality. Although anti-vascular endothelial growth factor drugs have shown great promise as a therapeutic target for treatment of advanced cervical cancer, drug resistance and class-specific side effects negat...

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Main Authors: Ping Yang, Na Chen, Dongyun Yang, Janet Crane, Bangxing Huang, Ruiqing Dong, Xiaoqing Yi, Jing Guo, Jing Cai, Zehua Wang
Format: Article
Language:English
Published: SAGE Publishing 2017-07-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317711658
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author Ping Yang
Na Chen
Dongyun Yang
Janet Crane
Bangxing Huang
Ruiqing Dong
Xiaoqing Yi
Jing Guo
Jing Cai
Zehua Wang
author_facet Ping Yang
Na Chen
Dongyun Yang
Janet Crane
Bangxing Huang
Ruiqing Dong
Xiaoqing Yi
Jing Guo
Jing Cai
Zehua Wang
author_sort Ping Yang
collection DOAJ
description Metastatic or recurrent cervical cancer has limited treatment options and a high rate of mortality. Although anti-vascular endothelial growth factor drugs have shown great promise as a therapeutic target for treatment of advanced cervical cancer, drug resistance and class-specific side effects negate long-term benefits. The identification of alternative anti-angiogenic factors will be critical for future drug development for advanced or recurrent cervical cancer. In this study, we found that angiopoietins and Tie receptors were highly expressed in cervical cancer cells. Tie-2 expression in tumor cells predicted poorer prognosis. Wound closure assay and Transwell assay showed that upregulated or downregulated Ang-1 and Ang-2 expression promoted or reduced cervical cancer cell lines migration and invasion, respectively. In subcutaneous xenograft models of cervical cancer, downregulation of Ang-1 and Ang-2 attenuated tumor growth. The expression of vimentin and endomucin and microvessel density were all significantly decreased in the siAng-1 group and siAng-2 group relative to the infection control group. Our data support that dual inhibition of Ang-1 and Ang-2 may be an alternative target for anti-angiogenic adjuvant therapy in advanced or recurrent cervical squamous cell cancer.
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series Tumor Biology
spelling doaj-art-1e9cf55e954f43edbcac34a57f1ac6b02025-07-02T03:38:07ZengSAGE PublishingTumor Biology1423-03802017-07-013910.1177/1010428317711658Cervical cancer cell–derived angiopoietins promote tumor progressionPing Yang0Na Chen1Dongyun Yang2Janet Crane3Bangxing Huang4Ruiqing Dong5Xiaoqing Yi6Jing Guo7Jing Cai8Zehua Wang9Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. ChinaDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. ChinaDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. ChinaDepartment of Obstetrics and Gynecology, Tianyou Hospital Attended to Wuhan University of Science and Technology, Wuhan, P.R. ChinaDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. ChinaDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. ChinaDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. ChinaDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. ChinaMetastatic or recurrent cervical cancer has limited treatment options and a high rate of mortality. Although anti-vascular endothelial growth factor drugs have shown great promise as a therapeutic target for treatment of advanced cervical cancer, drug resistance and class-specific side effects negate long-term benefits. The identification of alternative anti-angiogenic factors will be critical for future drug development for advanced or recurrent cervical cancer. In this study, we found that angiopoietins and Tie receptors were highly expressed in cervical cancer cells. Tie-2 expression in tumor cells predicted poorer prognosis. Wound closure assay and Transwell assay showed that upregulated or downregulated Ang-1 and Ang-2 expression promoted or reduced cervical cancer cell lines migration and invasion, respectively. In subcutaneous xenograft models of cervical cancer, downregulation of Ang-1 and Ang-2 attenuated tumor growth. The expression of vimentin and endomucin and microvessel density were all significantly decreased in the siAng-1 group and siAng-2 group relative to the infection control group. Our data support that dual inhibition of Ang-1 and Ang-2 may be an alternative target for anti-angiogenic adjuvant therapy in advanced or recurrent cervical squamous cell cancer.https://doi.org/10.1177/1010428317711658
spellingShingle Ping Yang
Na Chen
Dongyun Yang
Janet Crane
Bangxing Huang
Ruiqing Dong
Xiaoqing Yi
Jing Guo
Jing Cai
Zehua Wang
Cervical cancer cell–derived angiopoietins promote tumor progression
Tumor Biology
title Cervical cancer cell–derived angiopoietins promote tumor progression
title_full Cervical cancer cell–derived angiopoietins promote tumor progression
title_fullStr Cervical cancer cell–derived angiopoietins promote tumor progression
title_full_unstemmed Cervical cancer cell–derived angiopoietins promote tumor progression
title_short Cervical cancer cell–derived angiopoietins promote tumor progression
title_sort cervical cancer cell derived angiopoietins promote tumor progression
url https://doi.org/10.1177/1010428317711658
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AT nachen cervicalcancercellderivedangiopoietinspromotetumorprogression
AT dongyunyang cervicalcancercellderivedangiopoietinspromotetumorprogression
AT janetcrane cervicalcancercellderivedangiopoietinspromotetumorprogression
AT bangxinghuang cervicalcancercellderivedangiopoietinspromotetumorprogression
AT ruiqingdong cervicalcancercellderivedangiopoietinspromotetumorprogression
AT xiaoqingyi cervicalcancercellderivedangiopoietinspromotetumorprogression
AT jingguo cervicalcancercellderivedangiopoietinspromotetumorprogression
AT jingcai cervicalcancercellderivedangiopoietinspromotetumorprogression
AT zehuawang cervicalcancercellderivedangiopoietinspromotetumorprogression