Cargando…

Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer

Radiotherapy (RT) is a key player in the treatment of head and neck cancer (HNC). The RT response, however, is variable and influenced by multiple tumoral and tumor microenvironmental factors, such as human papillomavirus (HPV) infections and hypoxia. To investigate the biological mechanisms behind...

Descripción completa

Detalles Bibliográficos
Autores principales: Wegge, Marilyn, Dok, Rüveyda, Dubois, Ludwig J., Nuyts, Sandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963786/
https://www.ncbi.nlm.nih.gov/pubmed/36835181
http://dx.doi.org/10.3390/ijms24043763
_version_ 1784896340676837376
author Wegge, Marilyn
Dok, Rüveyda
Dubois, Ludwig J.
Nuyts, Sandra
author_facet Wegge, Marilyn
Dok, Rüveyda
Dubois, Ludwig J.
Nuyts, Sandra
author_sort Wegge, Marilyn
collection PubMed
description Radiotherapy (RT) is a key player in the treatment of head and neck cancer (HNC). The RT response, however, is variable and influenced by multiple tumoral and tumor microenvironmental factors, such as human papillomavirus (HPV) infections and hypoxia. To investigate the biological mechanisms behind these variable responses, preclinical models are crucial. Up till now, 2D clonogenic and in vivo assays have remained the gold standard, although the popularity of 3D models is rising. In this study, we investigate the use of 3D spheroid models as a preclinical tool for radiobiological research by comparing the RT response of two HPV-positive and two HPV-negative HNC spheroid models to the RT response of their corresponding 2D and in vivo models. We demonstrate that HPV-positive spheroids keep their higher intrinsic radiosensitivity when compared to HPV-negative spheroids. A good correlation is found in the RT response between HPV-positive SCC154 and HPV-negative CAL27 spheroids and their respective xenografts. In addition, 3D spheroids are able to capture the heterogeneity of RT responses within HPV-positive and HPV-negative models. Moreover, we demonstrate the potential use of 3D spheroids in the study of the mechanisms underlying these RT responses in a spatial manner by whole-mount Ki-67 and pimonidazole staining. Overall, our results show that 3D spheroids are a promising model to assess the RT response in HNC.
format Online
Article
Text
id pubmed-9963786
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-99637862023-02-26 Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer Wegge, Marilyn Dok, Rüveyda Dubois, Ludwig J. Nuyts, Sandra Int J Mol Sci Article Radiotherapy (RT) is a key player in the treatment of head and neck cancer (HNC). The RT response, however, is variable and influenced by multiple tumoral and tumor microenvironmental factors, such as human papillomavirus (HPV) infections and hypoxia. To investigate the biological mechanisms behind these variable responses, preclinical models are crucial. Up till now, 2D clonogenic and in vivo assays have remained the gold standard, although the popularity of 3D models is rising. In this study, we investigate the use of 3D spheroid models as a preclinical tool for radiobiological research by comparing the RT response of two HPV-positive and two HPV-negative HNC spheroid models to the RT response of their corresponding 2D and in vivo models. We demonstrate that HPV-positive spheroids keep their higher intrinsic radiosensitivity when compared to HPV-negative spheroids. A good correlation is found in the RT response between HPV-positive SCC154 and HPV-negative CAL27 spheroids and their respective xenografts. In addition, 3D spheroids are able to capture the heterogeneity of RT responses within HPV-positive and HPV-negative models. Moreover, we demonstrate the potential use of 3D spheroids in the study of the mechanisms underlying these RT responses in a spatial manner by whole-mount Ki-67 and pimonidazole staining. Overall, our results show that 3D spheroids are a promising model to assess the RT response in HNC. MDPI 2023-02-13 /pmc/articles/PMC9963786/ /pubmed/36835181 http://dx.doi.org/10.3390/ijms24043763 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wegge, Marilyn
Dok, Rüveyda
Dubois, Ludwig J.
Nuyts, Sandra
Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer
title Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer
title_full Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer
title_fullStr Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer
title_full_unstemmed Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer
title_short Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer
title_sort use of 3d spheroid models for the assessment of rt response in head and neck cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963786/
https://www.ncbi.nlm.nih.gov/pubmed/36835181
http://dx.doi.org/10.3390/ijms24043763
work_keys_str_mv AT weggemarilyn useof3dspheroidmodelsfortheassessmentofrtresponseinheadandneckcancer
AT dokruveyda useof3dspheroidmodelsfortheassessmentofrtresponseinheadandneckcancer
AT duboisludwigj useof3dspheroidmodelsfortheassessmentofrtresponseinheadandneckcancer
AT nuytssandra useof3dspheroidmodelsfortheassessmentofrtresponseinheadandneckcancer