Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.

Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the differen...

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Autores principales: Corine M Beaufort, Jean C A Helmijr, Anna M Piskorz, Marlous Hoogstraat, Kirsten Ruigrok-Ritstier, Nicolle Besselink, Muhammed Murtaza, Wilfred F J van IJcken, Anouk A J Heine, Marcel Smid, Marco J Koudijs, James D Brenton, Els M J J Berns, Jozien Helleman
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Publicado: Public Library of Science (PLoS) 2014
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Acceso en línea:https://doaj.org/article/89fef8c147544e4ca580af119453cff1
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spelling oai:doaj.org-article:89fef8c147544e4ca580af119453cff12021-11-25T06:00:15ZOvarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.1932-620310.1371/journal.pone.0103988https://doaj.org/article/89fef8c147544e4ca580af119453cff12014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0103988https://doaj.org/toc/1932-6203Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the different histological and molecular ovarian cancer subtypes is critical to enable reliable preclinical testing. There are approximately 100 publicly available ovarian cancer cell lines but their cellular and molecular characteristics are largely undescribed. We have characterized 39 ovarian cancer cell lines under uniform conditions for growth characteristics, mRNA/microRNA expression, exon sequencing, drug response for clinically-relevant therapeutics and collated all available information on the original clinical features and site of origin. We tested for statistical associations between the cellular and molecular features of the lines and clinical features. Of the 39 ovarian cancer cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes: Epithelial (n = 21), Round (n = 7) and Spindle (n = 12) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes in the Spindle subtype. Comparison with the original clinical data showed association of the spindle-like tumours with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the expression profiles of Spindle, Round and Epithelial morphologies clustered with the previously described C1-stromal, C5-mesenchymal and C4 ovarian subtype expression profiles respectively. Comprehensive profiling of 39 ovarian cancer cell lines under controlled, uniform conditions demonstrates clinically relevant cellular and genomic characteristics. This data provides a rational basis for selecting models to develop specific treatment approaches for histological and molecular subtypes of ovarian cancer.Corine M BeaufortJean C A HelmijrAnna M PiskorzMarlous HoogstraatKirsten Ruigrok-RitstierNicolle BesselinkMuhammed MurtazaWilfred F J van IJckenAnouk A J HeineMarcel SmidMarco J KoudijsJames D BrentonEls M J J BernsJozien HellemanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e103988 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Corine M Beaufort
Jean C A Helmijr
Anna M Piskorz
Marlous Hoogstraat
Kirsten Ruigrok-Ritstier
Nicolle Besselink
Muhammed Murtaza
Wilfred F J van IJcken
Anouk A J Heine
Marcel Smid
Marco J Koudijs
James D Brenton
Els M J J Berns
Jozien Helleman
Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
description Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the different histological and molecular ovarian cancer subtypes is critical to enable reliable preclinical testing. There are approximately 100 publicly available ovarian cancer cell lines but their cellular and molecular characteristics are largely undescribed. We have characterized 39 ovarian cancer cell lines under uniform conditions for growth characteristics, mRNA/microRNA expression, exon sequencing, drug response for clinically-relevant therapeutics and collated all available information on the original clinical features and site of origin. We tested for statistical associations between the cellular and molecular features of the lines and clinical features. Of the 39 ovarian cancer cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes: Epithelial (n = 21), Round (n = 7) and Spindle (n = 12) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes in the Spindle subtype. Comparison with the original clinical data showed association of the spindle-like tumours with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the expression profiles of Spindle, Round and Epithelial morphologies clustered with the previously described C1-stromal, C5-mesenchymal and C4 ovarian subtype expression profiles respectively. Comprehensive profiling of 39 ovarian cancer cell lines under controlled, uniform conditions demonstrates clinically relevant cellular and genomic characteristics. This data provides a rational basis for selecting models to develop specific treatment approaches for histological and molecular subtypes of ovarian cancer.
format article
author Corine M Beaufort
Jean C A Helmijr
Anna M Piskorz
Marlous Hoogstraat
Kirsten Ruigrok-Ritstier
Nicolle Besselink
Muhammed Murtaza
Wilfred F J van IJcken
Anouk A J Heine
Marcel Smid
Marco J Koudijs
James D Brenton
Els M J J Berns
Jozien Helleman
author_facet Corine M Beaufort
Jean C A Helmijr
Anna M Piskorz
Marlous Hoogstraat
Kirsten Ruigrok-Ritstier
Nicolle Besselink
Muhammed Murtaza
Wilfred F J van IJcken
Anouk A J Heine
Marcel Smid
Marco J Koudijs
James D Brenton
Els M J J Berns
Jozien Helleman
author_sort Corine M Beaufort
title Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
title_short Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
title_full Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
title_fullStr Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
title_full_unstemmed Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
title_sort ovarian cancer cell line panel (occp): clinical importance of in vitro morphological subtypes.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/89fef8c147544e4ca580af119453cff1
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