Speaker
Description
Invasion into surrounding tissues is a hallmark of cancer \cite{hanahan}. In contrast to individually migrating cells, multicellular clusters exhibit enhanced resistance to radiotherapy and DNA damage \cite{haeger}. In this work we seek to identify the mechanisms that generate the cell-cell contact patterns associated with collective therapy resistance using quantitative and mechanistic approaches.
We established a graph-based framework to quantify cell-cell contacts from confocal images of migrating cells in 3D collagen matrix stained for nuclei and actin. Cells are represented as nodes and inferred contacts as edges with weights derived from nuclear distance and contact length. Experimental datasets reveal condition-dependent shifts in neighbor number, clustering, and contact strength.
To uncover underlying mechanisms, we developed a Cellular Potts Model implemented in the simulation software Morpheus. The model incorporates cell–cell adhesion, active cellular motility, and interactions with the extracellular matrix. To enable direct comparison, we then analyzed simulation snapshots using the identical pipeline as for the experimental data.
Systematic variation of the model parameters shows that increased adhesion shifts network topology toward higher neighbor numbers and stronger connections, recapitulating experimental signatures. Hence we argue that our contact observables link contact-based phenotypes to specific biophysical drivers of collective resistance.
Bibliography
@article{hanahan,
title = {Hallmarks of cancer: The next generation},
volume = {144},
shorttitle = {Hallmarks of Cancer},
pages = {646--674},
journaltitle = {Cell},
shortjournal = {Cell},
author = {Hanahan, Douglas and Weinberg, Robert A.},
urldate = {2023-07-31},
date = {2011}
}
@article{haeger,
title = {Collective cancer invasion forms an integrin-dependent radioresistant niche},
volume = {217},
issn = {1540-9538},
pages = {e20181184},
journaltitle = {J Exp Med},
author = {Haeger, Anna and Alexander, Stephanie and Vullings, Manon and Kaiser, Fabian M. P. and Veelken, Cornelia and Flucke, Uta and Koehl, Gudrun E. and Hirschberg, Markus and Flentje, Michael and Hoffman, Robert M. and Geissler, Edward K. and Kissler, Stephan and Friedl, Peter},
date = {2020}
}
