Cargando…

Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma

BACKGROUND: Patient derived xenografts (PDX) are generated by transplanting the original patient’s tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade...

Descripción completa

Detalles Bibliográficos
Autores principales: Dong, Ruifen, Qiang, Wenan, Guo, Haiyang, Xu, Xiaofei, Kim, J. Julie, Mazar, Andrew, Kong, Beihua, Wei, Jian-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031262/
https://www.ncbi.nlm.nih.gov/pubmed/27655386
http://dx.doi.org/10.1186/s13045-016-0318-6
_version_ 1782454774380101632
author Dong, Ruifen
Qiang, Wenan
Guo, Haiyang
Xu, Xiaofei
Kim, J. Julie
Mazar, Andrew
Kong, Beihua
Wei, Jian-Jun
author_facet Dong, Ruifen
Qiang, Wenan
Guo, Haiyang
Xu, Xiaofei
Kim, J. Julie
Mazar, Andrew
Kong, Beihua
Wei, Jian-Jun
author_sort Dong, Ruifen
collection PubMed
description BACKGROUND: Patient derived xenografts (PDX) are generated by transplanting the original patient’s tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC) is a deadly form of ovarian/fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient. METHODS: In this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged (from P0 to P4) and tumors were grafted orthotopically under the ovarian bursa or subcutaneously. RESULTS: Comparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted. CONCLUSION: Our findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-016-0318-6) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5031262
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-50312622016-09-29 Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma Dong, Ruifen Qiang, Wenan Guo, Haiyang Xu, Xiaofei Kim, J. Julie Mazar, Andrew Kong, Beihua Wei, Jian-Jun J Hematol Oncol Research BACKGROUND: Patient derived xenografts (PDX) are generated by transplanting the original patient’s tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC) is a deadly form of ovarian/fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient. METHODS: In this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged (from P0 to P4) and tumors were grafted orthotopically under the ovarian bursa or subcutaneously. RESULTS: Comparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted. CONCLUSION: Our findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-016-0318-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-09-21 /pmc/articles/PMC5031262/ /pubmed/27655386 http://dx.doi.org/10.1186/s13045-016-0318-6 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Dong, Ruifen
Qiang, Wenan
Guo, Haiyang
Xu, Xiaofei
Kim, J. Julie
Mazar, Andrew
Kong, Beihua
Wei, Jian-Jun
Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma
title Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma
title_full Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma
title_fullStr Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma
title_full_unstemmed Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma
title_short Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma
title_sort histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031262/
https://www.ncbi.nlm.nih.gov/pubmed/27655386
http://dx.doi.org/10.1186/s13045-016-0318-6
work_keys_str_mv AT dongruifen histologicandmolecularanalysisofpatientderivedxenograftsofhighgradeserousovariancarcinoma
AT qiangwenan histologicandmolecularanalysisofpatientderivedxenograftsofhighgradeserousovariancarcinoma
AT guohaiyang histologicandmolecularanalysisofpatientderivedxenograftsofhighgradeserousovariancarcinoma
AT xuxiaofei histologicandmolecularanalysisofpatientderivedxenograftsofhighgradeserousovariancarcinoma
AT kimjjulie histologicandmolecularanalysisofpatientderivedxenograftsofhighgradeserousovariancarcinoma
AT mazarandrew histologicandmolecularanalysisofpatientderivedxenograftsofhighgradeserousovariancarcinoma
AT kongbeihua histologicandmolecularanalysisofpatientderivedxenograftsofhighgradeserousovariancarcinoma
AT weijianjun histologicandmolecularanalysisofpatientderivedxenograftsofhighgradeserousovariancarcinoma