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Clinically relevant morphological structures in breast cancer represent transcriptionally distinct tumor cell populations with varied degrees of epithelial-mesenchymal transition and CD44(+)CD24(-) stemness

Intratumor morphological heterogeneity in breast cancer is represented by different morphological structures (tubular, alveolar, solid, trabecular, and discrete) and contributes to poor prognosis; however, the mechanisms involved remain unclear. In this study, we performed 3D imaging, laser microdis...

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Autores principales: Denisov, Evgeny V., Skryabin, Nikolay A., Gerashchenko, Tatiana S., Tashireva, Lubov A., Wilhelm, Jochen, Buldakov, Mikhail A., Sleptcov, Aleksei A., Lebedev, Igor N., Vtorushin, Sergey V., Zavyalova, Marina V., Cherdyntseva, Nadezhda V., Perelmuter, Vladimir M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617414/
https://www.ncbi.nlm.nih.gov/pubmed/28977854
http://dx.doi.org/10.18632/oncotarget.18022
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author Denisov, Evgeny V.
Skryabin, Nikolay A.
Gerashchenko, Tatiana S.
Tashireva, Lubov A.
Wilhelm, Jochen
Buldakov, Mikhail A.
Sleptcov, Aleksei A.
Lebedev, Igor N.
Vtorushin, Sergey V.
Zavyalova, Marina V.
Cherdyntseva, Nadezhda V.
Perelmuter, Vladimir M.
author_facet Denisov, Evgeny V.
Skryabin, Nikolay A.
Gerashchenko, Tatiana S.
Tashireva, Lubov A.
Wilhelm, Jochen
Buldakov, Mikhail A.
Sleptcov, Aleksei A.
Lebedev, Igor N.
Vtorushin, Sergey V.
Zavyalova, Marina V.
Cherdyntseva, Nadezhda V.
Perelmuter, Vladimir M.
author_sort Denisov, Evgeny V.
collection PubMed
description Intratumor morphological heterogeneity in breast cancer is represented by different morphological structures (tubular, alveolar, solid, trabecular, and discrete) and contributes to poor prognosis; however, the mechanisms involved remain unclear. In this study, we performed 3D imaging, laser microdissection-assisted array comparative genomic hybridization and gene expression microarray analysis of different morphological structures and examined their association with the standard immunohistochemistry scorings and CD44(+)CD24(-) cancer stem cells. We found that the intratumor morphological heterogeneity is not associated with chromosomal aberrations. By contrast, morphological structures were characterized by specific gene expression profiles and signaling pathways and significantly differed in progesterone receptor and Ki-67 expression. Most importantly, we observed significant differences between structures in the number of expressed genes of the epithelial and mesenchymal phenotypes and the association with cancer invasion pathways. Tubular (tube-shaped) and alveolar (spheroid-shaped) structures were transcriptionally similar and demonstrated co-expression of epithelial and mesenchymal markers. Solid (large shapeless) structures retained epithelial features but demonstrated an increase in mesenchymal traits and collective cell migration hallmarks. Mesenchymal genes and cancer invasion pathways, as well as Ki-67 expression, were enriched in trabecular (one/two rows of tumor cells) and discrete groups (single cells and/or arrangements of 2-5 cells). Surprisingly, the number of CD44(+)CD24(-) cells was found to be the lowest in discrete groups and the highest in alveolar and solid structures. Overall, our findings indicate the association of intratumor morphological heterogeneity in breast cancer with the epithelial-mesenchymal transition and CD44(+)CD24(-) stemness and the appeal of this heterogeneity as a model for the study of cancer invasion.
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spelling pubmed-56174142017-10-03 Clinically relevant morphological structures in breast cancer represent transcriptionally distinct tumor cell populations with varied degrees of epithelial-mesenchymal transition and CD44(+)CD24(-) stemness Denisov, Evgeny V. Skryabin, Nikolay A. Gerashchenko, Tatiana S. Tashireva, Lubov A. Wilhelm, Jochen Buldakov, Mikhail A. Sleptcov, Aleksei A. Lebedev, Igor N. Vtorushin, Sergey V. Zavyalova, Marina V. Cherdyntseva, Nadezhda V. Perelmuter, Vladimir M. Oncotarget Research Paper Intratumor morphological heterogeneity in breast cancer is represented by different morphological structures (tubular, alveolar, solid, trabecular, and discrete) and contributes to poor prognosis; however, the mechanisms involved remain unclear. In this study, we performed 3D imaging, laser microdissection-assisted array comparative genomic hybridization and gene expression microarray analysis of different morphological structures and examined their association with the standard immunohistochemistry scorings and CD44(+)CD24(-) cancer stem cells. We found that the intratumor morphological heterogeneity is not associated with chromosomal aberrations. By contrast, morphological structures were characterized by specific gene expression profiles and signaling pathways and significantly differed in progesterone receptor and Ki-67 expression. Most importantly, we observed significant differences between structures in the number of expressed genes of the epithelial and mesenchymal phenotypes and the association with cancer invasion pathways. Tubular (tube-shaped) and alveolar (spheroid-shaped) structures were transcriptionally similar and demonstrated co-expression of epithelial and mesenchymal markers. Solid (large shapeless) structures retained epithelial features but demonstrated an increase in mesenchymal traits and collective cell migration hallmarks. Mesenchymal genes and cancer invasion pathways, as well as Ki-67 expression, were enriched in trabecular (one/two rows of tumor cells) and discrete groups (single cells and/or arrangements of 2-5 cells). Surprisingly, the number of CD44(+)CD24(-) cells was found to be the lowest in discrete groups and the highest in alveolar and solid structures. Overall, our findings indicate the association of intratumor morphological heterogeneity in breast cancer with the epithelial-mesenchymal transition and CD44(+)CD24(-) stemness and the appeal of this heterogeneity as a model for the study of cancer invasion. Impact Journals LLC 2017-05-19 /pmc/articles/PMC5617414/ /pubmed/28977854 http://dx.doi.org/10.18632/oncotarget.18022 Text en Copyright: © 2017 Denisov et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Denisov, Evgeny V.
Skryabin, Nikolay A.
Gerashchenko, Tatiana S.
Tashireva, Lubov A.
Wilhelm, Jochen
Buldakov, Mikhail A.
Sleptcov, Aleksei A.
Lebedev, Igor N.
Vtorushin, Sergey V.
Zavyalova, Marina V.
Cherdyntseva, Nadezhda V.
Perelmuter, Vladimir M.
Clinically relevant morphological structures in breast cancer represent transcriptionally distinct tumor cell populations with varied degrees of epithelial-mesenchymal transition and CD44(+)CD24(-) stemness
title Clinically relevant morphological structures in breast cancer represent transcriptionally distinct tumor cell populations with varied degrees of epithelial-mesenchymal transition and CD44(+)CD24(-) stemness
title_full Clinically relevant morphological structures in breast cancer represent transcriptionally distinct tumor cell populations with varied degrees of epithelial-mesenchymal transition and CD44(+)CD24(-) stemness
title_fullStr Clinically relevant morphological structures in breast cancer represent transcriptionally distinct tumor cell populations with varied degrees of epithelial-mesenchymal transition and CD44(+)CD24(-) stemness
title_full_unstemmed Clinically relevant morphological structures in breast cancer represent transcriptionally distinct tumor cell populations with varied degrees of epithelial-mesenchymal transition and CD44(+)CD24(-) stemness
title_short Clinically relevant morphological structures in breast cancer represent transcriptionally distinct tumor cell populations with varied degrees of epithelial-mesenchymal transition and CD44(+)CD24(-) stemness
title_sort clinically relevant morphological structures in breast cancer represent transcriptionally distinct tumor cell populations with varied degrees of epithelial-mesenchymal transition and cd44(+)cd24(-) stemness
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617414/
https://www.ncbi.nlm.nih.gov/pubmed/28977854
http://dx.doi.org/10.18632/oncotarget.18022
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