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Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix

The metaplastic epithelium of the transformation zone (TZ) including the squamocolumnar junction (SCJ) of the uterine cervix is a prime target of human papilloma virus (HPV) infection and subsequent cancer development. Due to the lack of adequate in vitro models for SCJ, however, investigations into...

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Autores principales: Maru, Yoshiaki, Kawata, Akira, Taguchi, Ayumi, Ishii, Yoshiyuki, Baba, Satoshi, Mori, Mayuyo, Nagamatsu, Takeshi, Oda, Katsutoshi, Kukimoto, Iwao, Osuga, Yutaka, Fujii, Tomoyuki, Hippo, Yoshitaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140077/
https://www.ncbi.nlm.nih.gov/pubmed/32183493
http://dx.doi.org/10.3390/cancers12030694
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author Maru, Yoshiaki
Kawata, Akira
Taguchi, Ayumi
Ishii, Yoshiyuki
Baba, Satoshi
Mori, Mayuyo
Nagamatsu, Takeshi
Oda, Katsutoshi
Kukimoto, Iwao
Osuga, Yutaka
Fujii, Tomoyuki
Hippo, Yoshitaka
author_facet Maru, Yoshiaki
Kawata, Akira
Taguchi, Ayumi
Ishii, Yoshiyuki
Baba, Satoshi
Mori, Mayuyo
Nagamatsu, Takeshi
Oda, Katsutoshi
Kukimoto, Iwao
Osuga, Yutaka
Fujii, Tomoyuki
Hippo, Yoshitaka
author_sort Maru, Yoshiaki
collection PubMed
description The metaplastic epithelium of the transformation zone (TZ) including the squamocolumnar junction (SCJ) of the uterine cervix is a prime target of human papilloma virus (HPV) infection and subsequent cancer development. Due to the lack of adequate in vitro models for SCJ, however, investigations into its physiological roles and vulnerability to carcinogenesis have been limited. By using Matrigel-based three-dimensional culture techniques, we propagated organoids derived from the normal SCJ region, along with metaplastic squamous cells in the TZ. Consisting predominantly of squamous cells, organoids basically exhibited a dense structure. However, at least in some organoids, a small but discrete population of mucin-producing endocervix cells co-existed adjacent to the squamous cell population, virtually recapitulating the configuration of SCJ in a TZ background. In addition, transcriptome analysis confirmed a higher expression level of many SCJ marker genes in organoids, compared to that in the immortalized cervical cell lines of non-SCJ origin. Thus, the obtained organoids appear to mimic cervical SCJ cells and, in particular, metaplastic squamous cells from the TZ, likely providing a novel platform in which HPV-driven cervical cancer development could be investigated.
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spelling pubmed-71400772020-04-13 Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix Maru, Yoshiaki Kawata, Akira Taguchi, Ayumi Ishii, Yoshiyuki Baba, Satoshi Mori, Mayuyo Nagamatsu, Takeshi Oda, Katsutoshi Kukimoto, Iwao Osuga, Yutaka Fujii, Tomoyuki Hippo, Yoshitaka Cancers (Basel) Article The metaplastic epithelium of the transformation zone (TZ) including the squamocolumnar junction (SCJ) of the uterine cervix is a prime target of human papilloma virus (HPV) infection and subsequent cancer development. Due to the lack of adequate in vitro models for SCJ, however, investigations into its physiological roles and vulnerability to carcinogenesis have been limited. By using Matrigel-based three-dimensional culture techniques, we propagated organoids derived from the normal SCJ region, along with metaplastic squamous cells in the TZ. Consisting predominantly of squamous cells, organoids basically exhibited a dense structure. However, at least in some organoids, a small but discrete population of mucin-producing endocervix cells co-existed adjacent to the squamous cell population, virtually recapitulating the configuration of SCJ in a TZ background. In addition, transcriptome analysis confirmed a higher expression level of many SCJ marker genes in organoids, compared to that in the immortalized cervical cell lines of non-SCJ origin. Thus, the obtained organoids appear to mimic cervical SCJ cells and, in particular, metaplastic squamous cells from the TZ, likely providing a novel platform in which HPV-driven cervical cancer development could be investigated. MDPI 2020-03-15 /pmc/articles/PMC7140077/ /pubmed/32183493 http://dx.doi.org/10.3390/cancers12030694 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
Maru, Yoshiaki
Kawata, Akira
Taguchi, Ayumi
Ishii, Yoshiyuki
Baba, Satoshi
Mori, Mayuyo
Nagamatsu, Takeshi
Oda, Katsutoshi
Kukimoto, Iwao
Osuga, Yutaka
Fujii, Tomoyuki
Hippo, Yoshitaka
Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix
title Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix
title_full Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix
title_fullStr Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix
title_full_unstemmed Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix
title_short Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix
title_sort establishment and molecular phenotyping of organoids from the squamocolumnar junction region of the uterine cervix
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140077/
https://www.ncbi.nlm.nih.gov/pubmed/32183493
http://dx.doi.org/10.3390/cancers12030694
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