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Comparative Molecular Analysis of Cancer Behavior Cultured In Vitro, In Vivo, and Ex Vivo

Current pre-clinical models of cancer fail to recapitulate the cancer cell behavior in primary tumors primarily because of the lack of a deeper understanding of the effects that the microenvironment has on cancer cell phenotype. Transcriptomic profiling of 4T1 murine mammary carcinoma cells from 2D...

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Autores principales: Hum, Nicholas R., Sebastian, Aimy, Gilmore, Sean F., He, Wei, Martin, Kelly A., Hinckley, Aubree, Dubbin, Karen R., Moya, Monica L., Wheeler, Elizabeth K., Coleman, Matthew A., Loots, Gabriela G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140030/
https://www.ncbi.nlm.nih.gov/pubmed/32183351
http://dx.doi.org/10.3390/cancers12030690
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author Hum, Nicholas R.
Sebastian, Aimy
Gilmore, Sean F.
He, Wei
Martin, Kelly A.
Hinckley, Aubree
Dubbin, Karen R.
Moya, Monica L.
Wheeler, Elizabeth K.
Coleman, Matthew A.
Loots, Gabriela G.
author_facet Hum, Nicholas R.
Sebastian, Aimy
Gilmore, Sean F.
He, Wei
Martin, Kelly A.
Hinckley, Aubree
Dubbin, Karen R.
Moya, Monica L.
Wheeler, Elizabeth K.
Coleman, Matthew A.
Loots, Gabriela G.
author_sort Hum, Nicholas R.
collection PubMed
description Current pre-clinical models of cancer fail to recapitulate the cancer cell behavior in primary tumors primarily because of the lack of a deeper understanding of the effects that the microenvironment has on cancer cell phenotype. Transcriptomic profiling of 4T1 murine mammary carcinoma cells from 2D and 3D cultures, subcutaneous or orthotopic allografts (from immunocompetent or immunodeficient mice), as well as ex vivo tumoroids, revealed differences in molecular signatures including altered expression of genes involved in cell cycle progression, cell signaling and extracellular matrix remodeling. The 3D culture platforms had more in vivo-like transcriptional profiles than 2D cultures. In vivo tumors had more cells undergoing epithelial-to-mesenchymal transition (EMT) while in vitro cultures had cells residing primarily in an epithelial or mesenchymal state. Ex vivo tumoroids incorporated aspects of in vivo and in vitro culturing, retaining higher abundance of cells undergoing EMT while shifting cancer cell fate towards a more mesenchymal state. Cellular heterogeneity surveyed by scRNA-seq revealed that ex vivo tumoroids, while rapidly expanding cancer and fibroblast populations, lose a significant proportion of immune components. This study emphasizes the need to improve in vitro culture systems and preserve syngeneic-like tumor composition by maintaining similar EMT heterogeneity as well as inclusion of stromal subpopulations.
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spelling pubmed-71400302020-04-13 Comparative Molecular Analysis of Cancer Behavior Cultured In Vitro, In Vivo, and Ex Vivo Hum, Nicholas R. Sebastian, Aimy Gilmore, Sean F. He, Wei Martin, Kelly A. Hinckley, Aubree Dubbin, Karen R. Moya, Monica L. Wheeler, Elizabeth K. Coleman, Matthew A. Loots, Gabriela G. Cancers (Basel) Article Current pre-clinical models of cancer fail to recapitulate the cancer cell behavior in primary tumors primarily because of the lack of a deeper understanding of the effects that the microenvironment has on cancer cell phenotype. Transcriptomic profiling of 4T1 murine mammary carcinoma cells from 2D and 3D cultures, subcutaneous or orthotopic allografts (from immunocompetent or immunodeficient mice), as well as ex vivo tumoroids, revealed differences in molecular signatures including altered expression of genes involved in cell cycle progression, cell signaling and extracellular matrix remodeling. The 3D culture platforms had more in vivo-like transcriptional profiles than 2D cultures. In vivo tumors had more cells undergoing epithelial-to-mesenchymal transition (EMT) while in vitro cultures had cells residing primarily in an epithelial or mesenchymal state. Ex vivo tumoroids incorporated aspects of in vivo and in vitro culturing, retaining higher abundance of cells undergoing EMT while shifting cancer cell fate towards a more mesenchymal state. Cellular heterogeneity surveyed by scRNA-seq revealed that ex vivo tumoroids, while rapidly expanding cancer and fibroblast populations, lose a significant proportion of immune components. This study emphasizes the need to improve in vitro culture systems and preserve syngeneic-like tumor composition by maintaining similar EMT heterogeneity as well as inclusion of stromal subpopulations. MDPI 2020-03-14 /pmc/articles/PMC7140030/ /pubmed/32183351 http://dx.doi.org/10.3390/cancers12030690 Text en © 2020 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
Hum, Nicholas R.
Sebastian, Aimy
Gilmore, Sean F.
He, Wei
Martin, Kelly A.
Hinckley, Aubree
Dubbin, Karen R.
Moya, Monica L.
Wheeler, Elizabeth K.
Coleman, Matthew A.
Loots, Gabriela G.
Comparative Molecular Analysis of Cancer Behavior Cultured In Vitro, In Vivo, and Ex Vivo
title Comparative Molecular Analysis of Cancer Behavior Cultured In Vitro, In Vivo, and Ex Vivo
title_full Comparative Molecular Analysis of Cancer Behavior Cultured In Vitro, In Vivo, and Ex Vivo
title_fullStr Comparative Molecular Analysis of Cancer Behavior Cultured In Vitro, In Vivo, and Ex Vivo
title_full_unstemmed Comparative Molecular Analysis of Cancer Behavior Cultured In Vitro, In Vivo, and Ex Vivo
title_short Comparative Molecular Analysis of Cancer Behavior Cultured In Vitro, In Vivo, and Ex Vivo
title_sort comparative molecular analysis of cancer behavior cultured in vitro, in vivo, and ex vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140030/
https://www.ncbi.nlm.nih.gov/pubmed/32183351
http://dx.doi.org/10.3390/cancers12030690
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