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Quantifying rates of cell migration and cell proliferation in co-culture barrier assays reveals how skin and melanoma cells interact during melanoma spreading and invasion

Parvathi Haridas, Catherine J. Penington, Jacqui A. McGovern, D. L. Sean McElwain, Matthew J. Simpson
doi: https://doi.org/10.1101/124842
Parvathi Haridas
aInstitute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove 4059, Australia.
bSchool of Mathematical Sciences, QUT, PO Box 2434, Brisbane 4001, Australia.
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Catherine J. Penington
bSchool of Mathematical Sciences, QUT, PO Box 2434, Brisbane 4001, Australia.
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Jacqui A. McGovern
aInstitute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove 4059, Australia.
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D. L. Sean McElwain
aInstitute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove 4059, Australia.
bSchool of Mathematical Sciences, QUT, PO Box 2434, Brisbane 4001, Australia.
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Matthew J. Simpson
aInstitute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Kelvin Grove 4059, Australia.
bSchool of Mathematical Sciences, QUT, PO Box 2434, Brisbane 4001, Australia.
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  • For correspondence: matthew.simpson@qut.edu.au
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ABSTRACT

Malignant spreading involves the migration of cancer cells amongst other native cell types. For example, in vivo melanoma invasion involves individual melanoma cells migrating through native skin, which is composed of several distinct subpopulations of cells. Here, we aim to quantify how interactions between melanoma and fibroblast cells affect the collective spreading of a heterogeneous population of these cells in vitro. We perform a suite of circular barrier assays that includes: (i) monoculture assays with fibroblast cells; (ii) monoculture assays with SK-MEL-28 melanoma cells; and (iii) a series of co-culture assays initiated with three different ratios of SK-MEL-28 melanoma cells and fibroblast cells. Using immunostaining, detailed cell density histograms are constructed to illustrate how the two subpopulations of cells are spatially arranged within the spreading heterogeneous population. Calibrating the solution of a continuum partial differential equation to the experimental results from the monoculture assays allows us to estimate the cell diffusivity and the cell proliferation rate for the melanoma and the fibroblast cells, separately. Using the parameter estimates from the monoculture assays, we then make a prediction of the spatial spreading in the co-culture assays. Results show that the parameter estimates obtained from the monoculture assays lead to a reasonably accurate prediction of the spatial arrangement of the two subpopulations in the co-culture assays. Overall, the spatial pattern of spreading of the melanoma cells and the fibroblast cells is very similar in monoculture and co-culture conditions. Therefore, we find no clear evidence of any interactions other than cell-to-cell contact and crowding effects.

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Posted April 19, 2017.
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Quantifying rates of cell migration and cell proliferation in co-culture barrier assays reveals how skin and melanoma cells interact during melanoma spreading and invasion
Parvathi Haridas, Catherine J. Penington, Jacqui A. McGovern, D. L. Sean McElwain, Matthew J. Simpson
bioRxiv 124842; doi: https://doi.org/10.1101/124842
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Quantifying rates of cell migration and cell proliferation in co-culture barrier assays reveals how skin and melanoma cells interact during melanoma spreading and invasion
Parvathi Haridas, Catherine J. Penington, Jacqui A. McGovern, D. L. Sean McElwain, Matthew J. Simpson
bioRxiv 124842; doi: https://doi.org/10.1101/124842

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