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Cited by 211Cervical Cancer and HPV ResearchCancer Cells and Metastasis3D Printing in Biomedical Research

Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer

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Lõhmussaar, Kadi, Oka, Rurika, Espejo Valle-Inclan, Jose, Smits, Milou H.H., Wardak, Hila, Korving, Jeroen, Begthel, Harry, Proost, Natalie +7 more·2021·Cell Stem Cell
DOI 10.1016/j.stem.2021.03.012
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Abstract

Cervical cancer is a common gynecological malignancy often caused by high-risk human papillomavirus. There is a paucity of human-derived culture systems to study the cervical epithelium and the cancers derived thereof. Here we describe a long-term culturing protocol for ecto- and endocervical epithelia that generates 3D organoids that stably recapitulate the two tissues of origin. As evidenced for HSV-1, organoid-based cervical models may serve to study sexually transmitted infections. Starting from Pap brush material, a small biobank of tumoroids derived from affected individuals was established that retained the causative human papillomavirus (HPV) genomes. One of these uniquely carried the poorly characterized HPV30 subtype, implying a potential role in carcinogenesis. The tumoroids displayed differential responses to common chemotherapeutic agents and grew as xenografts in mice. This study describes an experimental platform for cervical (cancer) research and for future personalized medicine approaches.

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References 75 · Cited by 211

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Authors
Lõhmussaar, K., Oka, R., Espejo Valle-Inclan, J., Smits, M. H. H., Wardak, H., Korving, J., Begthel, H., Proost, N., van de Ven, M., Kranenburg, O. W., Jonges, T. G. N., Zweemer, R. P., Veersema, S., van Boxtel, R., & Clevers, H.
Affiliations
  • Royal Netherlands Academy of Arts and Sciences (NL)
  • Oncode Institute (NL)
  • The Netherlands Cancer Institute (NL)
  • Utrecht University (NL)
  • University Medical Center Utrecht (NL)
Corresponding author
Clevers, Hans
ORCID
Venue
Cell Stem Cell
Publisher
Elsevier BV
Published
2021-08
Volume
28
Issue
8
Pages
1380-1396.e6
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
DOI
10.1016/j.stem.2021.03.012
OpenAlex
W3155510140
Cited by
211
References
75
Citations by year
2026: 45 · 2025: 38 · 2024: 43 · 2023: 45 · 2022: 26 · 2021: 13 · 2016: 1
FWCI
23.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Topics
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
cervical cancer, human papillomavirus, viral oncogenesis, ectocervical epithelium, endocervical epithelium, herpes simplex virus type 1, sexually transmitted infections, tumor organoids, chemoresistance, xenografts, personalized medicine
MeSH terms
Animals, Uterine Cervical Neoplasms, Epithelium, Female, Humans, Organoids, Papillomaviridae, Mice, Carcinogenesis

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