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Three-dimensional experiments and individual based simulations show that cell proliferation drives melanoma nest formation in human skin tissue

Parvathi Haridas, Alexander P. Browning, Jacqui A. McGovern, D.L. Sean McElwain, View ORCID ProfileMatthew J. Simpson
doi: https://doi.org/10.1101/244582
Parvathi Haridas
1Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove 4059, Australia.
2School of Mathematical Sciences, QUT, Brisbane 4001, Australia.
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Alexander P. Browning
2School of Mathematical Sciences, QUT, Brisbane 4001, Australia.
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Jacqui A. McGovern
1Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove 4059, Australia.
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D.L. Sean McElwain
1Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove 4059, Australia.
2School of Mathematical Sciences, QUT, Brisbane 4001, Australia.
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Matthew J. Simpson
1Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove 4059, Australia.
2School of Mathematical Sciences, QUT, Brisbane 4001, Australia.
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  • ORCID record for Matthew J. Simpson
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Abstract

Background Melanoma can be diagnosed by identifying nests of cells on the skin surface. Understanding the processes that drive nest formation is important as these processes could be potential targets for new cancer drugs. Cell proliferation and cell migration are two potential mechanisms that could conceivably drive melanoma nest formation. However, it is unclear which one of these two putative mechanisms plays a dominant role in driving nest formation.

Results We use a suite of three-dimensional (3D) experiments in human skin tissue and a parallel series of 3D individual-based simulations to explore whether cell migration or cell proliferation plays a dominant role in nest formation. In the experiments we measure nest formation in populations of irradiated (non-proliferative) and non-irradiated (proliferative) melanoma cells, cultured together with primary keratinocyte and fibroblast cells on a 3D experimental human skin model. Results show that nest size depends on initial cell number and is driven primarily by cell proliferation rather than cell migration.

Conclusions We find that nest size depends on initial cell number, and is driven primarily by cell proliferation rather than cell migration. All experimental results are consistent with simulation data from a 3D individual based model (IBM) of cell migration and cell proliferation.

Footnotes

  • ↵* matthew.simpson{at}qut.edu.au

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 08, 2018.
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Three-dimensional experiments and individual based simulations show that cell proliferation drives melanoma nest formation in human skin tissue
Parvathi Haridas, Alexander P. Browning, Jacqui A. McGovern, D.L. Sean McElwain, Matthew J. Simpson
bioRxiv 244582; doi: https://doi.org/10.1101/244582
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Three-dimensional experiments and individual based simulations show that cell proliferation drives melanoma nest formation in human skin tissue
Parvathi Haridas, Alexander P. Browning, Jacqui A. McGovern, D.L. Sean McElwain, Matthew J. Simpson
bioRxiv 244582; doi: https://doi.org/10.1101/244582

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