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  • Melanoma mutations modify melanocyte dynamics in co-culture with keratinocytes or fibroblasts

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    Gabrielli318948Published.pdf (8.229Mb)
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    Version of Record (VoR)
    Author(s)
    Škalamera, D
    Stevenson, AJ
    Ehmann, A
    Ainger, SA
    Lanagan, C
    Sturm, RA
    Gabrielli, B
    Griffith University Author(s)
    Gabrielli, Brian
    Year published
    2019
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    Abstract
    Melanocytic cell interactions are integral to skin homeostasis, and affect the outcome of multiple diseases, including cutaneous pigmentation disorders and melanoma. By using automated-microscopy and machine-learning-assisted morphology analysis of primary human melanocytes in co-culture, we performed combinatorial interrogation of melanocyte genotypic variants and functional assessment of lentivirus-introduced mutations. Keratinocyte-induced melanocyte dendricity, an indicator of melanocyte differentiation, was reduced in the melanocortin 1 receptor (MC1R) R/R variant strain and by NRAS.Q61K and BRAF.V600E expression, while ...
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    Melanocytic cell interactions are integral to skin homeostasis, and affect the outcome of multiple diseases, including cutaneous pigmentation disorders and melanoma. By using automated-microscopy and machine-learning-assisted morphology analysis of primary human melanocytes in co-culture, we performed combinatorial interrogation of melanocyte genotypic variants and functional assessment of lentivirus-introduced mutations. Keratinocyte-induced melanocyte dendricity, an indicator of melanocyte differentiation, was reduced in the melanocortin 1 receptor (MC1R) R/R variant strain and by NRAS.Q61K and BRAF.V600E expression, while expression of CDK4.R24C and RAC1.P29S had no detectable effect. Time-lapse tracking of melanocytes in co-culture revealed dynamic interaction phenotypes and hyper-motile cell states that indicated that, in addition to the known role in activating mitogenic signalling, MEK-pathway-activating mutations may also allow melanocytes to escape keratinocyte control and increase their invasive potential. Expanding this combinatorial platform will identify other therapeutic target mutations and melanocyte genetic variants, as well as increase understanding of skin cell interactions.
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    Journal Title
    Journal of Cell Science
    Volume
    132
    Issue
    24
    DOI
    https://doi.org/10.1242/jcs.234716
    Copyright Statement
    © 2019. Company of Biologists Ltd. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
    Subject
    Biological sciences
    Biomedical and clinical sciences
    Fibroblasts
    High-content-imaging
    Keratinocytes
    Melanocytes
    Melanoma
    Publication URI
    http://hdl.handle.net/10072/396277
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    • Journal articles

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