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

Kadi Lõhmussaar, Rurika Oka, Jose Espejo Valle-Inclan, Milou H H Smits, Hila Wardak, Jeroen Korving, Harry Begthel, Natalie Proost, Marieke van de Ven, Onno W Kranenburg, Trudy G N Jonges, Ronald P Zweemer, Sebastiaan Veersema, Ruben van Boxtel, Hans Clevers

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1380-1396.e6
JournalCell stem cell
Volume28
Issue number8
DOIs
Publication statusPublished - 5 Aug 2021

Keywords

  • Animals
  • Carcinogenesis
  • Epithelium
  • Female
  • Humans
  • Mice
  • Organoids
  • Papillomaviridae
  • Uterine Cervical Neoplasms

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