Establishment and Molecular Phenotyping of Organoids from the Squamocolumnar Junction Region of the Uterine Cervix
Open Access
- 15 March 2020
- Vol. 12 (3), 694
- https://doi.org/10.3390/cancers12030694
Abstract
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.Keywords
Funding Information
- Japan Agency for Medical Research and Development (19fm0208013h0003 and 19fm0208013h0203)
This publication has 38 references indexed in Scilit:
- Incidence and clearance of oral human papillomavirus infection in men: the HIM cohort studyThe Lancet, 2013
- A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancerProceedings of the National Academy of Sciences of the United States of America, 2012
- Residual Embryonic Cells as Precursors of a Barrett's-like MetaplasiaCell, 2011
- Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publicationInternational Journal of Cancer, 2010
- Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal nicheNature, 2009
- Role of hormone cofactors in the human papillomavirus-induced carcinogenesis of the uterine cervixMolecular and Cellular Endocrinology, 2007
- Human Papillomavirus Type 16 E1 ∧ E4 Contributes to Multiple Facets of the Papillomavirus Life CycleJournal of Virology, 2005
- Normal Growth and Differentiation in a Spontaneously Immortalized Near-Diploid Human Keratinocyte Cell Line, NIKSJournal of Investigative Dermatology, 2000
- Generation of Papillomavirus-Immortalized Cell Lines from Normal Human Ectocervical, Endocervical, and Vaginal Epithelium that Maintain Expression of Tissue-Specific Differentiation Proteins1Biology of Reproduction, 1997
- ORIGINAL SITE OF CERVICAL CARCINOMA. TOPOGRAPHICAL RELATIONSHIP OF CARCINOMA OF THE CERVIX TO THE EXTERNAL OS AND TO THE SQUAMOCOLUMNAR JUNCTIONObstetrical & Gynecological Survey, 1957