Initial cell density encodes proliferative potential in cancer cell populations
Abstract Individual cells exhibit specific proliferative responses to changes in microenvironmental conditions. Whether such potential is constrained by the cell density throughout the growth process is however unclear. Here, we identify a theoretical framework that captures how the information enco...
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2021-03-01
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Online Access: | https://doi.org/10.1038/s41598-021-85406-z |
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doaj-2cad83971b2c45e29d0e3d3554b472782021-03-21T12:38:28ZengNature Publishing GroupScientific Reports2045-23222021-03-0111111110.1038/s41598-021-85406-zInitial cell density encodes proliferative potential in cancer cell populationsChiara Enrico Bena0Marco Del Giudice1Alice Grob2Thomas Gueudré3Mattia Miotto4Dimitra Gialama5Matteo Osella6Emilia Turco7Francesca Ceroni8Andrea De Martino9Carla Bosia10CNRS, Institut de Biologie Paris-Seine (IBPS), Laboratoire Jean Perrin (LJP), Sorbonne UniversitéIIGM - Italian Institute for Genomic Medicine, c/o IRCCSDepartment of Life Sciences, Imperial College LondonIIGM - Italian Institute for Genomic Medicine, c/o IRCCSDepartment of Physics, Sapienza UniversityDepartment of Chemical Engineering, Imperial College LondonPhysics Department and INFN, University of TurinMolecular Biotechnology Center, University of TurinDepartment of Chemical Engineering, Imperial College LondonIIGM - Italian Institute for Genomic Medicine, c/o IRCCSIIGM - Italian Institute for Genomic Medicine, c/o IRCCSAbstract Individual cells exhibit specific proliferative responses to changes in microenvironmental conditions. Whether such potential is constrained by the cell density throughout the growth process is however unclear. Here, we identify a theoretical framework that captures how the information encoded in the initial density of cancer cell populations impacts their growth profile. By following the growth of hundreds of populations of cancer cells, we found that the time they need to adapt to the environment decreases as the initial cell density increases. Moreover, the population growth rate shows a maximum at intermediate initial densities. With the support of a mathematical model, we show that the observed interdependence of adaptation time and growth rate is significantly at odds both with standard logistic growth models and with the Monod-like function that governs the dependence of the growth rate on nutrient levels. Our results (i) uncover and quantify a previously unnoticed heterogeneity in the growth dynamics of cancer cell populations; (ii) unveil how population growth may be affected by single-cell adaptation times; (iii) contribute to our understanding of the clinically-observed dependence of the primary and metastatic tumor take rates on the initial density of implanted cancer cells.https://doi.org/10.1038/s41598-021-85406-z |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chiara Enrico Bena Marco Del Giudice Alice Grob Thomas Gueudré Mattia Miotto Dimitra Gialama Matteo Osella Emilia Turco Francesca Ceroni Andrea De Martino Carla Bosia |
spellingShingle |
Chiara Enrico Bena Marco Del Giudice Alice Grob Thomas Gueudré Mattia Miotto Dimitra Gialama Matteo Osella Emilia Turco Francesca Ceroni Andrea De Martino Carla Bosia Initial cell density encodes proliferative potential in cancer cell populations Scientific Reports |
author_facet |
Chiara Enrico Bena Marco Del Giudice Alice Grob Thomas Gueudré Mattia Miotto Dimitra Gialama Matteo Osella Emilia Turco Francesca Ceroni Andrea De Martino Carla Bosia |
author_sort |
Chiara Enrico Bena |
title |
Initial cell density encodes proliferative potential in cancer cell populations |
title_short |
Initial cell density encodes proliferative potential in cancer cell populations |
title_full |
Initial cell density encodes proliferative potential in cancer cell populations |
title_fullStr |
Initial cell density encodes proliferative potential in cancer cell populations |
title_full_unstemmed |
Initial cell density encodes proliferative potential in cancer cell populations |
title_sort |
initial cell density encodes proliferative potential in cancer cell populations |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-03-01 |
description |
Abstract Individual cells exhibit specific proliferative responses to changes in microenvironmental conditions. Whether such potential is constrained by the cell density throughout the growth process is however unclear. Here, we identify a theoretical framework that captures how the information encoded in the initial density of cancer cell populations impacts their growth profile. By following the growth of hundreds of populations of cancer cells, we found that the time they need to adapt to the environment decreases as the initial cell density increases. Moreover, the population growth rate shows a maximum at intermediate initial densities. With the support of a mathematical model, we show that the observed interdependence of adaptation time and growth rate is significantly at odds both with standard logistic growth models and with the Monod-like function that governs the dependence of the growth rate on nutrient levels. Our results (i) uncover and quantify a previously unnoticed heterogeneity in the growth dynamics of cancer cell populations; (ii) unveil how population growth may be affected by single-cell adaptation times; (iii) contribute to our understanding of the clinically-observed dependence of the primary and metastatic tumor take rates on the initial density of implanted cancer cells. |
url |
https://doi.org/10.1038/s41598-021-85406-z |
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