Journal Article

DKFZ-2025-00324

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A Unique Signature for Cancer-Associated Fibroblasts in Melanoma Metastases.

Tauch, S. (First author)DKFZ* ; Hey, J.DKFZ* ; Walter, B.DKFZ* ; Gengenbacher, N.DKFZ* ; Weiß, L.DKFZ* ; Sator-Schmitt, M.DKFZ* ; Lohr, S.DKFZ* ; Brobeil, A. ; Schirmacher, P. ; Utikal, J.DKFZ* ; Augustin, H. G.DKFZ* ; Plass, C.DKFZ* ; Angel, P. (Last author)DKFZ*

2025
Wiley-Blackwell Oxford [u.a.]

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Please use a persistent id in citations: doi: DOI:10.1111/pcmr.70002   doi:DOI:10.1111/pcmr.70002

Abstract: 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.

Keyword(s): Cancer-Associated Fibroblasts: pathology (MeSH) ; Cancer-Associated Fibroblasts: metabolism (MeSH) ; Melanoma: pathology (MeSH) ; Melanoma: genetics (MeSH) ; Humans (MeSH) ; Animals (MeSH) ; Mice (MeSH) ; Tumor Microenvironment (MeSH) ; Gene Expression Regulation, Neoplastic (MeSH) ; Neoplasm Metastasis (MeSH) ; Lung Neoplasms: pathology (MeSH) ; Lung Neoplasms: secondary (MeSH) ; Lung Neoplasms: genetics (MeSH) ; Mice, Inbred C57BL (MeSH) ; Cell Line, Tumor (MeSH) ; Signal Transduction (MeSH) ; CAF ; SAA ; melanoma ; metastasis ; scRNA sequencing

Note: #EA:A100#LA:A100 / DKFZ-ZMBH Alliance

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Contributing Institute(s):

1. Signaltransduktion/ Wachstumskontrolle (A100)
2. Epigenomik (B370)
3. A190 Vaskuläre Onkologie und Metastasierung (A190)
4. KKE Dermatoonkologie (A370)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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