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Inference of glioblastoma migration and proliferation rates using single time-point images

Cancer cell migration is a driving mechanism of invasion in solid malignant tumors. Anti-migratory treatments provide an alternative approach for managing disease progression. However, we currently lack scalable screening methods for identifying novel anti-migratory drugs. To this end, we develop a...

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Autores principales: Rosén, Emil, Mangukiya, Hitesh Bhagavanbhai, Elfineh, Ludmila, Stockgard, Rebecka, Krona, Cecilia, Gerlee, Philip, Nelander, Sven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10102065/
https://www.ncbi.nlm.nih.gov/pubmed/37055469
http://dx.doi.org/10.1038/s42003-023-04750-0
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author Rosén, Emil
Mangukiya, Hitesh Bhagavanbhai
Elfineh, Ludmila
Stockgard, Rebecka
Krona, Cecilia
Gerlee, Philip
Nelander, Sven
author_facet Rosén, Emil
Mangukiya, Hitesh Bhagavanbhai
Elfineh, Ludmila
Stockgard, Rebecka
Krona, Cecilia
Gerlee, Philip
Nelander, Sven
author_sort Rosén, Emil
collection PubMed
description Cancer cell migration is a driving mechanism of invasion in solid malignant tumors. Anti-migratory treatments provide an alternative approach for managing disease progression. However, we currently lack scalable screening methods for identifying novel anti-migratory drugs. To this end, we develop a method that can estimate cell motility from single end-point images in vitro by estimating differences in the spatial distribution of cells and inferring proliferation and diffusion parameters using agent-based modeling and approximate Bayesian computation. To test the power of our method, we use it to investigate drug responses in a collection of 41 patient-derived glioblastoma cell cultures, identifying migration-associated pathways and drugs with potent anti-migratory effects. We validate our method and result in both in silico and in vitro using time-lapse imaging. Our proposed method applies to standard drug screen experiments, with no change needed, and emerges as a scalable approach to screen for anti-migratory drugs.
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spelling pubmed-101020652023-04-15 Inference of glioblastoma migration and proliferation rates using single time-point images Rosén, Emil Mangukiya, Hitesh Bhagavanbhai Elfineh, Ludmila Stockgard, Rebecka Krona, Cecilia Gerlee, Philip Nelander, Sven Commun Biol Article Cancer cell migration is a driving mechanism of invasion in solid malignant tumors. Anti-migratory treatments provide an alternative approach for managing disease progression. However, we currently lack scalable screening methods for identifying novel anti-migratory drugs. To this end, we develop a method that can estimate cell motility from single end-point images in vitro by estimating differences in the spatial distribution of cells and inferring proliferation and diffusion parameters using agent-based modeling and approximate Bayesian computation. To test the power of our method, we use it to investigate drug responses in a collection of 41 patient-derived glioblastoma cell cultures, identifying migration-associated pathways and drugs with potent anti-migratory effects. We validate our method and result in both in silico and in vitro using time-lapse imaging. Our proposed method applies to standard drug screen experiments, with no change needed, and emerges as a scalable approach to screen for anti-migratory drugs. Nature Publishing Group UK 2023-04-13 /pmc/articles/PMC10102065/ /pubmed/37055469 http://dx.doi.org/10.1038/s42003-023-04750-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Rosén, Emil
Mangukiya, Hitesh Bhagavanbhai
Elfineh, Ludmila
Stockgard, Rebecka
Krona, Cecilia
Gerlee, Philip
Nelander, Sven
Inference of glioblastoma migration and proliferation rates using single time-point images
title Inference of glioblastoma migration and proliferation rates using single time-point images
title_full Inference of glioblastoma migration and proliferation rates using single time-point images
title_fullStr Inference of glioblastoma migration and proliferation rates using single time-point images
title_full_unstemmed Inference of glioblastoma migration and proliferation rates using single time-point images
title_short Inference of glioblastoma migration and proliferation rates using single time-point images
title_sort inference of glioblastoma migration and proliferation rates using single time-point images
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10102065/
https://www.ncbi.nlm.nih.gov/pubmed/37055469
http://dx.doi.org/10.1038/s42003-023-04750-0
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