A quantitative characterization of the heterogeneous response of glioblastoma U-87 MG cell line to temozolomide
Abstract Most cancers are genetically and phenotypically heterogeneous. This includes subpopulations of cells with different levels of sensitivity to chemotherapy, which may lead to treatment failure as the more resistant cells can survive drug treatment and continue to proliferate. While the geneti...
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Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-99426-6 |
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| author | Pragyesh Dixit Ilyas Djafer-Cherif Saumil Shah Karolina Drabik Arne Traulsen Bartlomiej Waclaw |
| author_facet | Pragyesh Dixit Ilyas Djafer-Cherif Saumil Shah Karolina Drabik Arne Traulsen Bartlomiej Waclaw |
| author_sort | Pragyesh Dixit |
| collection | DOAJ |
| description | Abstract Most cancers are genetically and phenotypically heterogeneous. This includes subpopulations of cells with different levels of sensitivity to chemotherapy, which may lead to treatment failure as the more resistant cells can survive drug treatment and continue to proliferate. While the genetic basis of resistance to many drugs is relatively well characterised, non-genetic factors are much less understood. Here we investigate the role of non-genetic, phenotypic heterogeneity in the response of glioblastoma cancer cells to the drug temozolomide (TMZ) often used to treat this type of cancer. Using a combination of live imaging, machine-learning image analysis and agent-based modelling, we show that even if all cells share the same genetic background, individual cells respond differently to TMZ. We quantitatively characterise this response by measuring the doubling time, lifespan, cell cycle phase, area and motility of cells, and determine how these quantities correlate with each other as well as between the mother and daughter cell. We also show that these responses do not correlate with the cellular level of the enzyme MGMT which has been implicated in the response to TMZ. |
| format | Article |
| id | doaj-art-446fd3612ba04a01be8c277e23bcb9ef |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-446fd3612ba04a01be8c277e23bcb9ef2025-08-20T01:49:39ZengNature PortfolioScientific Reports2045-23222025-05-0115111310.1038/s41598-025-99426-6A quantitative characterization of the heterogeneous response of glioblastoma U-87 MG cell line to temozolomidePragyesh Dixit0Ilyas Djafer-Cherif1Saumil Shah2Karolina Drabik3Arne Traulsen4Bartlomiej Waclaw5Dioscuri Centre for Physics and Chemistry of Bacteria, Institute of Physical Chemistry, Polish Academy of SciencesDioscuri Centre for Physics and Chemistry of Bacteria, Institute of Physical Chemistry, Polish Academy of SciencesDepartment of Theoretical Biology, Max Planck Institute for Evolutionary BiologyDioscuri Centre for Physics and Chemistry of Bacteria, Institute of Physical Chemistry, Polish Academy of SciencesDepartment of Theoretical Biology, Max Planck Institute for Evolutionary BiologyDioscuri Centre for Physics and Chemistry of Bacteria, Institute of Physical Chemistry, Polish Academy of SciencesAbstract Most cancers are genetically and phenotypically heterogeneous. This includes subpopulations of cells with different levels of sensitivity to chemotherapy, which may lead to treatment failure as the more resistant cells can survive drug treatment and continue to proliferate. While the genetic basis of resistance to many drugs is relatively well characterised, non-genetic factors are much less understood. Here we investigate the role of non-genetic, phenotypic heterogeneity in the response of glioblastoma cancer cells to the drug temozolomide (TMZ) often used to treat this type of cancer. Using a combination of live imaging, machine-learning image analysis and agent-based modelling, we show that even if all cells share the same genetic background, individual cells respond differently to TMZ. We quantitatively characterise this response by measuring the doubling time, lifespan, cell cycle phase, area and motility of cells, and determine how these quantities correlate with each other as well as between the mother and daughter cell. We also show that these responses do not correlate with the cellular level of the enzyme MGMT which has been implicated in the response to TMZ.https://doi.org/10.1038/s41598-025-99426-6CancerGlioblastomaTemozolomidePhenotypic heterogeneityMathematical modelling |
| spellingShingle | Pragyesh Dixit Ilyas Djafer-Cherif Saumil Shah Karolina Drabik Arne Traulsen Bartlomiej Waclaw A quantitative characterization of the heterogeneous response of glioblastoma U-87 MG cell line to temozolomide Scientific Reports Cancer Glioblastoma Temozolomide Phenotypic heterogeneity Mathematical modelling |
| title | A quantitative characterization of the heterogeneous response of glioblastoma U-87 MG cell line to temozolomide |
| title_full | A quantitative characterization of the heterogeneous response of glioblastoma U-87 MG cell line to temozolomide |
| title_fullStr | A quantitative characterization of the heterogeneous response of glioblastoma U-87 MG cell line to temozolomide |
| title_full_unstemmed | A quantitative characterization of the heterogeneous response of glioblastoma U-87 MG cell line to temozolomide |
| title_short | A quantitative characterization of the heterogeneous response of glioblastoma U-87 MG cell line to temozolomide |
| title_sort | quantitative characterization of the heterogeneous response of glioblastoma u 87 mg cell line to temozolomide |
| topic | Cancer Glioblastoma Temozolomide Phenotypic heterogeneity Mathematical modelling |
| url | https://doi.org/10.1038/s41598-025-99426-6 |
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