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

Autor:	Škalamera D; Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, 4102 QLD, Australia d.skalamera@uq.edu.au., Stevenson AJ; Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, 4102 QLD, Australia., Ehmann A; Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, 4102 QLD, Australia., Ainger SA; Dermatology Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, 4102 QLD, Australia., Lanagan C; Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, 4102 QLD, Australia., Sturm RA; Dermatology Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, 4102 QLD, Australia., Gabrielli B; Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, 4102 QLD, Australia.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2019 Dec 13; Vol. 132 (24). Date of Electronic Publication: 2019 Dec 13.
DOI:	10.1242/jcs.234716
Abstrakt:	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. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2019. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu