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Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression

The cancer testis antigen sperm protein 17 (Sp17) is a promising antigenic target in epithelial ovarian cancer (EOC) vaccine development. However, its role in ovarian cancer is unclear. We isolated and expanded Sp17(+) and Sp17(−) clones from the murine EOC cell line ID8, and compared their in-vitro...

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Autores principales: Gao, Qian, Xiang, Sue D., Wilson, Kirsty, Madondo, Mutsa, Stephens, Andrew N., Plebanski, Magdalena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115966/
https://www.ncbi.nlm.nih.gov/pubmed/30127274
http://dx.doi.org/10.3390/cancers10080276
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author Gao, Qian
Xiang, Sue D.
Wilson, Kirsty
Madondo, Mutsa
Stephens, Andrew N.
Plebanski, Magdalena
author_facet Gao, Qian
Xiang, Sue D.
Wilson, Kirsty
Madondo, Mutsa
Stephens, Andrew N.
Plebanski, Magdalena
author_sort Gao, Qian
collection PubMed
description The cancer testis antigen sperm protein 17 (Sp17) is a promising antigenic target in epithelial ovarian cancer (EOC) vaccine development. However, its role in ovarian cancer is unclear. We isolated and expanded Sp17(+) and Sp17(−) clones from the murine EOC cell line ID8, and compared their in-vitro cell growth characteristics and in-vivo tumorigenicity. We also examined the potential co-expression of molecules that may influence cancer cell survival and interaction with immune cells. These include stimulatory and immunosuppressive molecules, such as major histocompatibility class I molecules (MHC I), MHC II, cytotoxic T lymphocyte associated antigen-4 (CTLA-4), CD73, CD39, tumor necrosis factor receptor II (TNFRII), signal transducer and activator of transcription 3 (STAT3) and programmed death-ligand 1 (PD-L1). Whilst the presence of Sp17 was not correlated with the ID8 cell proliferation/growth capacity in vitro, it was critical to enable progressive tumor formation in vivo. Flow cytometry revealed that Sp17(+) ID8 cells displayed higher expression of both STAT3 and PD-L1, whilst MHC II expression was lower. Moreover, Sp17(high) (PD-L1(+)MHCII(−)) cell populations showed significantly enhanced resistance to Paclitaxel-induced cell death in vitro compared to Sp17(low) (PD-L1(−)MHCII(+)) cells, which was associated in turn with increased STAT3 expression. Together, the data support Sp17 as a factor associated with in-vivo tumor progression and chemo-resistance, validating it as a suitable target for vaccine development.
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spelling pubmed-61159662018-08-31 Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression Gao, Qian Xiang, Sue D. Wilson, Kirsty Madondo, Mutsa Stephens, Andrew N. Plebanski, Magdalena Cancers (Basel) Article The cancer testis antigen sperm protein 17 (Sp17) is a promising antigenic target in epithelial ovarian cancer (EOC) vaccine development. However, its role in ovarian cancer is unclear. We isolated and expanded Sp17(+) and Sp17(−) clones from the murine EOC cell line ID8, and compared their in-vitro cell growth characteristics and in-vivo tumorigenicity. We also examined the potential co-expression of molecules that may influence cancer cell survival and interaction with immune cells. These include stimulatory and immunosuppressive molecules, such as major histocompatibility class I molecules (MHC I), MHC II, cytotoxic T lymphocyte associated antigen-4 (CTLA-4), CD73, CD39, tumor necrosis factor receptor II (TNFRII), signal transducer and activator of transcription 3 (STAT3) and programmed death-ligand 1 (PD-L1). Whilst the presence of Sp17 was not correlated with the ID8 cell proliferation/growth capacity in vitro, it was critical to enable progressive tumor formation in vivo. Flow cytometry revealed that Sp17(+) ID8 cells displayed higher expression of both STAT3 and PD-L1, whilst MHC II expression was lower. Moreover, Sp17(high) (PD-L1(+)MHCII(−)) cell populations showed significantly enhanced resistance to Paclitaxel-induced cell death in vitro compared to Sp17(low) (PD-L1(−)MHCII(+)) cells, which was associated in turn with increased STAT3 expression. Together, the data support Sp17 as a factor associated with in-vivo tumor progression and chemo-resistance, validating it as a suitable target for vaccine development. MDPI 2018-08-20 /pmc/articles/PMC6115966/ /pubmed/30127274 http://dx.doi.org/10.3390/cancers10080276 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gao, Qian
Xiang, Sue D.
Wilson, Kirsty
Madondo, Mutsa
Stephens, Andrew N.
Plebanski, Magdalena
Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression
title Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression
title_full Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression
title_fullStr Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression
title_full_unstemmed Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression
title_short Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression
title_sort sperm protein 17 expression by murine epithelial ovarian cancer cells and its impact on tumor progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115966/
https://www.ncbi.nlm.nih.gov/pubmed/30127274
http://dx.doi.org/10.3390/cancers10080276
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