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Proteomic Profiling of a Mouse Model for Ovarian Granulosa Cell Tumor Identifies VCP as a Highly Sensitive Serum Tumor Marker in Several Human Cancers
The initial aim of this study was to identify novel serum diagnostic markers for the human ovarian granulosa cell tumor (GCT), a tumor that represents up to 5% of all ovarian cancers. To circumvent the paucity of human tissues available for analyses, we used the Ctnnb1 (tm1Mmt/+);Pten (tm1Hwu/tmiHwu...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411637/ https://www.ncbi.nlm.nih.gov/pubmed/22870330 http://dx.doi.org/10.1371/journal.pone.0042470 |
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author | Laguë, Marie-Noëlle Romieu-Mourez, Raphaëlle Bonneil, Éric Boyer, Alexandre Pouletty, Nicolas Mes-Masson, Anne-Marie Thibault, Pierre Nadeau, Marie-Ève Boerboom, Derek |
author_facet | Laguë, Marie-Noëlle Romieu-Mourez, Raphaëlle Bonneil, Éric Boyer, Alexandre Pouletty, Nicolas Mes-Masson, Anne-Marie Thibault, Pierre Nadeau, Marie-Ève Boerboom, Derek |
author_sort | Laguë, Marie-Noëlle |
collection | PubMed |
description | The initial aim of this study was to identify novel serum diagnostic markers for the human ovarian granulosa cell tumor (GCT), a tumor that represents up to 5% of all ovarian cancers. To circumvent the paucity of human tissues available for analyses, we used the Ctnnb1 (tm1Mmt/+);Pten (tm1Hwu/tmiHwu);Amhr2 (tm3(cre)Bhr/+) transgenic mouse model, which features the constitutive activation of CTNNB1 signaling combined with the loss of Pten in granulosa cells and develops GCTs that mimic aggressive forms of the human disease. Proteomic profiling by mass spectrometry showed that vinculin, enolase 1, several heat shock proteins, and valosin containing protein (VCP) were more abundantly secreted by cultured mouse GCT cells compared to primary cultured GC. Among these proteins, only VCP was present in significantly increased levels in the preoperative serum of GCT cancer patients compared to normal subjects. To determine the specificity of VCP, serum levels were also measured in ovarian carcinoma, non-Hodgkin's lymphoma and breast, colon, pancreatic, lung, and prostate cancer patients. Increased serum VCP levels were observed in the majority of cancer cases, with the exception of patients with lung or prostate cancer. Moreover, serum VCP levels were increased in some GCT, ovarian carcinoma, breast cancer, and colon cancer patients who did not otherwise display increased levels of widely used serum tumor markers for their cancer type (e.g. inhibin A, inhibin B, CA125, CEA, or CA15.3). These results demonstrate the potential use of VCP as highly sensitive serum marker for GCT as well as several other human cancers. |
format | Online Article Text |
id | pubmed-3411637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34116372012-08-06 Proteomic Profiling of a Mouse Model for Ovarian Granulosa Cell Tumor Identifies VCP as a Highly Sensitive Serum Tumor Marker in Several Human Cancers Laguë, Marie-Noëlle Romieu-Mourez, Raphaëlle Bonneil, Éric Boyer, Alexandre Pouletty, Nicolas Mes-Masson, Anne-Marie Thibault, Pierre Nadeau, Marie-Ève Boerboom, Derek PLoS One Research Article The initial aim of this study was to identify novel serum diagnostic markers for the human ovarian granulosa cell tumor (GCT), a tumor that represents up to 5% of all ovarian cancers. To circumvent the paucity of human tissues available for analyses, we used the Ctnnb1 (tm1Mmt/+);Pten (tm1Hwu/tmiHwu);Amhr2 (tm3(cre)Bhr/+) transgenic mouse model, which features the constitutive activation of CTNNB1 signaling combined with the loss of Pten in granulosa cells and develops GCTs that mimic aggressive forms of the human disease. Proteomic profiling by mass spectrometry showed that vinculin, enolase 1, several heat shock proteins, and valosin containing protein (VCP) were more abundantly secreted by cultured mouse GCT cells compared to primary cultured GC. Among these proteins, only VCP was present in significantly increased levels in the preoperative serum of GCT cancer patients compared to normal subjects. To determine the specificity of VCP, serum levels were also measured in ovarian carcinoma, non-Hodgkin's lymphoma and breast, colon, pancreatic, lung, and prostate cancer patients. Increased serum VCP levels were observed in the majority of cancer cases, with the exception of patients with lung or prostate cancer. Moreover, serum VCP levels were increased in some GCT, ovarian carcinoma, breast cancer, and colon cancer patients who did not otherwise display increased levels of widely used serum tumor markers for their cancer type (e.g. inhibin A, inhibin B, CA125, CEA, or CA15.3). These results demonstrate the potential use of VCP as highly sensitive serum marker for GCT as well as several other human cancers. Public Library of Science 2012-08-01 /pmc/articles/PMC3411637/ /pubmed/22870330 http://dx.doi.org/10.1371/journal.pone.0042470 Text en © 2012 Laguë et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Laguë, Marie-Noëlle Romieu-Mourez, Raphaëlle Bonneil, Éric Boyer, Alexandre Pouletty, Nicolas Mes-Masson, Anne-Marie Thibault, Pierre Nadeau, Marie-Ève Boerboom, Derek Proteomic Profiling of a Mouse Model for Ovarian Granulosa Cell Tumor Identifies VCP as a Highly Sensitive Serum Tumor Marker in Several Human Cancers |
title | Proteomic Profiling of a Mouse Model for Ovarian Granulosa Cell Tumor Identifies VCP as a Highly Sensitive Serum Tumor Marker in Several Human Cancers |
title_full | Proteomic Profiling of a Mouse Model for Ovarian Granulosa Cell Tumor Identifies VCP as a Highly Sensitive Serum Tumor Marker in Several Human Cancers |
title_fullStr | Proteomic Profiling of a Mouse Model for Ovarian Granulosa Cell Tumor Identifies VCP as a Highly Sensitive Serum Tumor Marker in Several Human Cancers |
title_full_unstemmed | Proteomic Profiling of a Mouse Model for Ovarian Granulosa Cell Tumor Identifies VCP as a Highly Sensitive Serum Tumor Marker in Several Human Cancers |
title_short | Proteomic Profiling of a Mouse Model for Ovarian Granulosa Cell Tumor Identifies VCP as a Highly Sensitive Serum Tumor Marker in Several Human Cancers |
title_sort | proteomic profiling of a mouse model for ovarian granulosa cell tumor identifies vcp as a highly sensitive serum tumor marker in several human cancers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411637/ https://www.ncbi.nlm.nih.gov/pubmed/22870330 http://dx.doi.org/10.1371/journal.pone.0042470 |
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