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Density-dependent migration characteristics of cancer cells driven by pseudopod coordination

View ORCID ProfileGerhard A. Burger, View ORCID ProfileBob van de Water, View ORCID ProfileSylvia E. Le Dévédec, View ORCID ProfileJoost B. Beltman
doi: https://doi.org/10.1101/2021.11.04.467267
Gerhard A. Burger
Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
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Bob van de Water
Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
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Sylvia E. Le Dévédec
Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
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Joost B. Beltman
Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
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  • For correspondence: j.b.beltman@lacdr.leidenuniv.nl
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Abstract

The ability of cancer cells to invade neighboring tissue from primary tumors is an important determinant of metastatic behavior. Quantification of cell migration characteristics such as migration speed and persistence helps to understand the requirements for such invasiveness. One factor that may influence invasion is how local tumor cell density shapes cell migration characteristics, which we here investigate with a combined experimental and computational modeling approach. First, we generated and analyzed time-lapse imaging data on two aggressive Triple-Negative Breast Cancer (TNBC) cell lines, HCC38 and Hs578T, during 2D migration assays at various cell densities. HCC38 cells exhibited a counter-intuitive increase in speed and persistence with increasing density, whereas Hs578T did not exhibit such an increase. Moreover, HCC38 cells exhibited strong cluster formation with active pseudopod-driven migration, especially at low densities, whereas Hs578T cells maintained a dispersed positioning. In order to obtain a mechanistic understanding of the density-dependent cell migration characteristics and cluster formation, we developed realistic spatial simulations using a Cellular Potts Model (CPM) with an explicit description of pseudopod dynamics. Model analysis demonstrated that strong coordination between pseudopods within single cells could explain the experimentally observed increase in speed and persistence with increasing density in HCC38 cells. Thus, the density-dependent migratory behavior could be an emergent property of single-cell characteristics without the need for additional mechanisms. This implies that coordination amongst pseudopods may play a role in the aggressive nature of cancers through mediating dispersal.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://doi.org/10.5281/zenodo.5484491

  • https://doi.org/10.5281/zenodo.5607734

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 04, 2021.
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Density-dependent migration characteristics of cancer cells driven by pseudopod coordination
Gerhard A. Burger, Bob van de Water, Sylvia E. Le Dévédec, Joost B. Beltman
bioRxiv 2021.11.04.467267; doi: https://doi.org/10.1101/2021.11.04.467267
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Density-dependent migration characteristics of cancer cells driven by pseudopod coordination
Gerhard A. Burger, Bob van de Water, Sylvia E. Le Dévédec, Joost B. Beltman
bioRxiv 2021.11.04.467267; doi: https://doi.org/10.1101/2021.11.04.467267

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