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Low Expression of Protocadherin-8 Promotes the Progression of Ovarian Cancer

OBJECTIVE: Ovarian cancer (OC) is the second most lethal gynecological cancer among women throughout the world. Protocadherin-8 (PCDH8) could function as a candidate tumor suppressor. However, the link between PCDH8 and OC development is poorly understood. MATERIALS AND METHODS: A total of 68 OC pat...

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Autores principales: Cao, Yuan, Yu, Yan, Chen, Xiaolong, Ren, Fang, Zhang, Ruitao, Jia, Yanyan, Ren, Zhigang, Sun, Ranran, Li, Juan, Shi, Huirong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794251/
https://www.ncbi.nlm.nih.gov/pubmed/29324532
http://dx.doi.org/10.1097/IGC.0000000000001169
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author Cao, Yuan
Yu, Yan
Chen, Xiaolong
Ren, Fang
Zhang, Ruitao
Jia, Yanyan
Ren, Zhigang
Sun, Ranran
Li, Juan
Shi, Huirong
author_facet Cao, Yuan
Yu, Yan
Chen, Xiaolong
Ren, Fang
Zhang, Ruitao
Jia, Yanyan
Ren, Zhigang
Sun, Ranran
Li, Juan
Shi, Huirong
author_sort Cao, Yuan
collection PubMed
description OBJECTIVE: Ovarian cancer (OC) is the second most lethal gynecological cancer among women throughout the world. Protocadherin-8 (PCDH8) could function as a candidate tumor suppressor. However, the link between PCDH8 and OC development is poorly understood. MATERIALS AND METHODS: A total of 68 OC patients were retrospectively enrolled. Clinical information was collected and cancer tissues were used for tissue microarray. The PCDH8 expression was determined on tissue microarray by immunohistochemical staining, and PCDH8 protein was detected in cancer tissues and adjacent tissue by western blotting. Human OC cell lines (SKOV-3 and OVCAR-3) were used to assess the effects of PCDH8 overexpression by western blot and real-time PCR analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay, wound healing migration assay, colony formation assay and invasion assays were performed to assess the influence of PCDH8 on cell function. Cells with Luc-nonspecific Lentiviral or Luc-Lentiviral with PCDH8 gene were subcutaneously injected into nude mice to observe the effect of PCDH8 gene on tumor growth. Bioluminescence imaging was used to observe tumor volume. RESULTS: We found a low expression of PCDH8 in OC tissues versus the corresponding adjacent tissue. The PCDH8 expression, International Federation of Gynecology and Obstetrics stage, metastasis and recurrence were the independent prognostic factors for over-all survival by multivariate analyses. Furthermore, the patients with recurrence presented a low level of PCDH8 in OC tissues, and patients with advanced tumor stage also had a low PCDH8 expression. Importantly, the low expression of PCDH8 in OC tissues had a poor prognosis with a low overall survival rate. Overexpression of PCDH8 could inhibit OC cell growth/proliferation, migration, invasion, and colony formation in vitro. In vivo experiments also proved that overexpression of PCDH8 could inhibit OC cell growth/proliferation. CONCLUSIONS: Protocadherin-8 might be considered as a candidate tumor suppressor and play a crucial role in the progression of OC.
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spelling pubmed-57942512018-02-13 Low Expression of Protocadherin-8 Promotes the Progression of Ovarian Cancer Cao, Yuan Yu, Yan Chen, Xiaolong Ren, Fang Zhang, Ruitao Jia, Yanyan Ren, Zhigang Sun, Ranran Li, Juan Shi, Huirong Int J Gynecol Cancer Basic Science OBJECTIVE: Ovarian cancer (OC) is the second most lethal gynecological cancer among women throughout the world. Protocadherin-8 (PCDH8) could function as a candidate tumor suppressor. However, the link between PCDH8 and OC development is poorly understood. MATERIALS AND METHODS: A total of 68 OC patients were retrospectively enrolled. Clinical information was collected and cancer tissues were used for tissue microarray. The PCDH8 expression was determined on tissue microarray by immunohistochemical staining, and PCDH8 protein was detected in cancer tissues and adjacent tissue by western blotting. Human OC cell lines (SKOV-3 and OVCAR-3) were used to assess the effects of PCDH8 overexpression by western blot and real-time PCR analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay, wound healing migration assay, colony formation assay and invasion assays were performed to assess the influence of PCDH8 on cell function. Cells with Luc-nonspecific Lentiviral or Luc-Lentiviral with PCDH8 gene were subcutaneously injected into nude mice to observe the effect of PCDH8 gene on tumor growth. Bioluminescence imaging was used to observe tumor volume. RESULTS: We found a low expression of PCDH8 in OC tissues versus the corresponding adjacent tissue. The PCDH8 expression, International Federation of Gynecology and Obstetrics stage, metastasis and recurrence were the independent prognostic factors for over-all survival by multivariate analyses. Furthermore, the patients with recurrence presented a low level of PCDH8 in OC tissues, and patients with advanced tumor stage also had a low PCDH8 expression. Importantly, the low expression of PCDH8 in OC tissues had a poor prognosis with a low overall survival rate. Overexpression of PCDH8 could inhibit OC cell growth/proliferation, migration, invasion, and colony formation in vitro. In vivo experiments also proved that overexpression of PCDH8 could inhibit OC cell growth/proliferation. CONCLUSIONS: Protocadherin-8 might be considered as a candidate tumor suppressor and play a crucial role in the progression of OC. Lippincott Williams & Wilkins 2018-02 2018-01-10 /pmc/articles/PMC5794251/ /pubmed/29324532 http://dx.doi.org/10.1097/IGC.0000000000001169 Text en Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of IGCS and ESGO. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Basic Science
Cao, Yuan
Yu, Yan
Chen, Xiaolong
Ren, Fang
Zhang, Ruitao
Jia, Yanyan
Ren, Zhigang
Sun, Ranran
Li, Juan
Shi, Huirong
Low Expression of Protocadherin-8 Promotes the Progression of Ovarian Cancer
title Low Expression of Protocadherin-8 Promotes the Progression of Ovarian Cancer
title_full Low Expression of Protocadherin-8 Promotes the Progression of Ovarian Cancer
title_fullStr Low Expression of Protocadherin-8 Promotes the Progression of Ovarian Cancer
title_full_unstemmed Low Expression of Protocadherin-8 Promotes the Progression of Ovarian Cancer
title_short Low Expression of Protocadherin-8 Promotes the Progression of Ovarian Cancer
title_sort low expression of protocadherin-8 promotes the progression of ovarian cancer
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794251/
https://www.ncbi.nlm.nih.gov/pubmed/29324532
http://dx.doi.org/10.1097/IGC.0000000000001169
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