3D tumour spheroids for the prediction of the effects of radiation and hyperthermia treatments.
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Date
2020-02-03Author
Brüningk, SC
Rivens, I
Box, C
Oelfke, U
Ter Haar, G
Type
Journal Article
Metadata
Show full item recordAbstract
For multimodality therapies such as the combination of hyperthermia and radiation, quantification of biological effects is key for dose prescription and response prediction. Tumour spheroids have a microenvironment that more closely resembles that of tumours in vivo and may thus be a superior in vitro cancer model than monolayer cultures. Here, the response of tumour spheroids formed from two established human cancer cell lines (HCT116 and CAL27) to single and combination treatments of radiation (0-20 Gy), and hyperthermia at 47 °C (0-780 CEM43) has been evaluated. Response was analysed in terms of spheroid growth, cell viability and the distribution of live/dead cells. Time-lapse imaging was used to evaluate mechanisms of cell death and cell detachment. It was found that sensitivity to heat in spheroids was significantly less than that seen in monolayer cultures. Spheroids showed different patterns of shrinkage and regrowth when exposed to heat or radiation: heated spheroids shed dead cells within four days of heating and displayed faster growth post-exposure than samples that received radiation or no treatment. Irradiated spheroids maintained a dense structure and exhibited a longer growth delay than spheroids receiving hyperthermia or combination treatment at (thermal) doses that yielded equivalent levels of clonogenic cell survival. We suggest that, unlike radiation, which kills dividing cells, hyperthermia-induced cell death affects cells independent of their proliferation status. This induces microenvironmental changes that promote spheroid growth. In conclusion, 3D tumour spheroid growth studies reveal differences in response to heat and/or radiation that were not apparent in 2D clonogenic assays but that may significantly influence treatment efficacy.
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Subject
Cell Line, Tumor
HCT116 Cells
Spheroids, Cellular
Humans
Neoplasms
Combined Modality Therapy
Hyperthermia, Induced
Tumor Stem Cell Assay
Dose-Response Relationship, Radiation
Cell Proliferation
Cell Survival
Models, Biological
Tumor Microenvironment
Research team
Radiotherapy Physics Modelling
Therapeutic Ultrasound
Language
eng
Date accepted
2020-01-17
License start date
2020-02-03
Citation
Scientific reports, 2020, 10 (1), pp. 1653 - ?
Publisher
NATURE PUBLISHING GROUP