TY  - JOUR
AU  - Tauch, Saskia
AU  - Hey, Joschka
AU  - Walter, Bettina
AU  - Gengenbacher, Nicolas
AU  - Weiß, Lena
AU  - Sator-Schmitt, Melanie
AU  - Lohr, Sabrina
AU  - Brobeil, Alexander
AU  - Schirmacher, Peter
AU  - Utikal, Jochen
AU  - Augustin, Hellmut G
AU  - Plass, Christoph
AU  - Angel, Peter
TI  - A Unique Signature for Cancer-Associated Fibroblasts in Melanoma Metastases.
JO  - Pigment cell & melanoma research
VL  - 38
IS  - 2
SN  - 1755-1471
CY  - Oxford [u.a.]
PB  - Wiley-Blackwell
M1  - DKFZ-2025-00324
SP  - e70002
PY  - 2025
N1  - #EA:A100#LA:A100  / DKFZ-ZMBH Alliance
AB  - 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.
KW  - Cancer-Associated Fibroblasts: pathology
KW  - Cancer-Associated Fibroblasts: metabolism
KW  - Melanoma: pathology
KW  - Melanoma: genetics
KW  - Humans
KW  - Animals
KW  - Mice
KW  - Tumor Microenvironment
KW  - Gene Expression Regulation, Neoplastic
KW  - Neoplasm Metastasis
KW  - Lung Neoplasms: pathology
KW  - Lung Neoplasms: secondary
KW  - Lung Neoplasms: genetics
KW  - Mice, Inbred C57BL
KW  - Cell Line, Tumor
KW  - Signal Transduction
KW  - CAF (Other)
KW  - SAA (Other)
KW  - melanoma (Other)
KW  - metastasis (Other)
KW  - scRNA sequencing (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39924882
DO  - DOI:DOI:10.1111/pcmr.70002
UR  - https://inrepo02.dkfz.de/record/298624
ER  -