A unique signature for cancer-associated fibroblasts in melanoma metastases

Cancer-associated fibroblasts (CAFs) represent a central cell population of the tumor microenvironment (TME). Recently, single-cell RNA-sequencing (scRNA-seq) analyses of primary tumors of different cancer entities yielded different classifications of CAF subsets underscoring the heterogeneity of CA...

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Main Authors: Tauch, Saskia (Author) , Hey, Joschka (Author) , Kast, Bettina (Author) , Gengenbacher, Nicolas (Author) , Weiß, Lena (Author) , Sator-Schmitt, Melanie (Author) , Lohr, Sabrina (Author) , Brobeil, Alexander (Author) , Schirmacher, Peter (Author) , Utikal, Jochen (Author) , Augustin, Hellmut (Author) , Plass, Christoph (Author) , Angel, Peter (Author)
Format: Article (Journal)
Language:English
Published: March 2025
In: Pigment cell & melanoma research
Year: 2025, Volume: 38, Issue: 2, Pages: 1-9
ISSN:1755-148X
DOI:10.1111/pcmr.70002
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1111/pcmr.70002
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/pcmr.70002
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Author Notes:Saskia Tauch, Joschka Hey, Bettina Kast, Nicolas Gengenbacher, Lena Weiß, Melanie Sator-Schmitt, Sabrina Lohr, Alexander Brobeil, Peter Schirmacher, Jochen Utikal, Hellmut G. Augustin, Christoph Plass, Peter Angel
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Summary:Cancer-associated fibroblasts (CAFs) represent a central cell population of the tumor microenvironment (TME). Recently, single-cell RNA-sequencing (scRNA-seq) analyses of primary tumors of different cancer entities yielded different classifications of CAF subsets underscoring the heterogeneity of CAFs within the TME. Here, we analyzed the transcriptional signatures of approximately 8400 CAFs and normal fibroblasts by scRNA-seq and compared genetic profiles of CAFs from murine melanoma primary tumors to CAFs from corresponding melanoma lung metastases. This revealed distinct subsets for primary tumor and metastasis-specific CAF populations, respectively. Combined with the spatial characterization of metastasis CAFs at the RNA and protein level, scRNA analyses indicate tumor-dependent crosstalk between neutrophils and CAFs, mediated via SAA3 and IL1b-related signaling pathways, which can be recapitulated in vitro. Analyzing tissue sections of human patient samples, this interaction was found to be present in human melanoma metastasis. Taken together, our data highlight unique characteristics of metastasis CAFs with potential therapeutic impact for melanoma metastasis.
Item Description:Online veröffentlicht: 9. Februar 2025
Gesehen am 18.06.2025
Physical Description:Online Resource
ISSN:1755-148X
DOI:10.1111/pcmr.70002