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

doi:10.1016/j.stem.2021.03.012

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

116 Citations (Scopus)

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 language	English
Pages (from-to)	1380-1396.e6
Journal	Cell Stem Cell
Volume	28
Issue number	8
DOIs	https://doi.org/10.1016/j.stem.2021.03.012
Publication status	Published - 05 Aug 2021

Keywords

Animals
Carcinogenesis
Epithelium
Female
Humans
Mice
Organoids
Papillomaviridae
Uterine Cervical Neoplasms

Access to Document

10.1016/j.stem.2021.03.012

Cite this

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. (2021). Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer. Cell Stem Cell, 28(8), 1380-1396.e6. https://doi.org/10.1016/j.stem.2021.03.012

@article{2ac5a620c347436eab5f719f1b6c1e2e,

title = "Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer",

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.",

keywords = "Animals, Carcinogenesis, Epithelium, Female, Humans, Mice, Organoids, Papillomaviridae, Uterine Cervical Neoplasms",

author = "Kadi L{\~o}hmussaar and Rurika Oka and {Espejo Valle-Inclan}, Jose and Smits, {Milou H H} and Hila Wardak and Jeroen Korving and Harry Begthel and Natalie Proost and {van de Ven}, Marieke and Kranenburg, {Onno W} and Jonges, {Trudy G N} and Zweemer, {Ronald P} and Sebastiaan Veersema and {van Boxtel}, Ruben and Hans Clevers",

year = "2021",

month = aug,

day = "5",

doi = "10.1016/j.stem.2021.03.012",

language = "English",

volume = "28",

pages = "1380--1396.e6",

journal = "Cell Stem Cell",

issn = "1934-5909",

publisher = "Cell Press",

number = "8",

}

Lõhmussaar, K, Oka, R, Espejo Valle-Inclan, J, Smits, MHH, Wardak, H, Korving, J, Begthel, H, Proost, N, van de Ven, M, Kranenburg, OW, Jonges, TGN, Zweemer, RP, Veersema, S, van Boxtel, R & Clevers, H 2021, 'Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer', Cell Stem Cell, vol. 28, no. 8, pp. 1380-1396.e6. https://doi.org/10.1016/j.stem.2021.03.012

TY - JOUR

T1 - Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer

AU - Lõhmussaar, Kadi

AU - Oka, Rurika

AU - Espejo Valle-Inclan, Jose

AU - Smits, Milou H H

AU - Wardak, Hila

AU - Korving, Jeroen

AU - Begthel, Harry

AU - Proost, Natalie

AU - van de Ven, Marieke

AU - Kranenburg, Onno W

AU - Jonges, Trudy G N

AU - Zweemer, Ronald P

AU - Veersema, Sebastiaan

AU - van Boxtel, Ruben

AU - Clevers, Hans

PY - 2021/8/5

Y1 - 2021/8/5

N2 - 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.

AB - 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.

KW - Animals

KW - Carcinogenesis

KW - Epithelium

KW - Female

KW - Humans

KW - Mice

KW - Organoids

KW - Papillomaviridae

KW - Uterine Cervical Neoplasms

U2 - 10.1016/j.stem.2021.03.012

DO - 10.1016/j.stem.2021.03.012

M3 - Article

C2 - 33852917

SN - 1934-5909

VL - 28

SP - 1380-1396.e6

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 8

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this