Prostate cancer cells converge to an inflammatory-like state upon metastatic dissemination

Identifying drivers of cancer progression to guide treatment selection is hindered by our limited understanding of tumor heterogeneity and its impact on tumor evolution. Here, we delineate the phenotypic variability across ~300,000 cells collected from multiple tumor loci in primary prostate and matched locoregional metastases using single-cell chromatin accessibility and gene expression sequencing. We find inter-patient heterogeneity to be confined to malignant populations. Within individual tumor loci, we see phenotypic heterogeneity among malignant cell populations despite a shared clonal genotypic architecture. We also observe that malignant cell populations disseminating to locoregional lymph nodes mirror the clonal architecture and phenotypic heterogeneity across primary tumor loci, while shifting from canonical prostate-cancer states to non-canonical inflammatory-like states. Our findings suggest a bottleneck imposed during the dissemination process, funneling prostate cancer cells toward an inflammatory-like cell state. These insights into the interplay between phenotypic identity and clonal architecture refine our understanding of prostate cancer progression and suggest that convergence of cancer cells towards an inflammatory-like state underlies dissemination to lymph nodes, offering a critical framework for future studies into prostate cancer metastatic potential.

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Publication Details

Journal
Nature Communications
Published
2025-12-23
DOI
https://doi.org/10.1038/s41467-025-67856-5
Citations
1
Primary Topic
Single-cell and spatial transcriptomics
Type
article
Field-Weighted Citation Impact
0.81

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article

Prostate cancer cells converge to an inflammatory-like state upon metastatic dissemination

Mathieu Lupien, Faizan Hasan, S. Minner, Tina Keshavarzian et al.
1 citations
Nature Communications
Single-cell and spatial transcriptomics
0.81
article

Prostate cancer cells converge to an inflammatory-like state upon metastatic dissemination

Mathieu Lupien, Faizan Hasan, S. Minner, Tina Keshavarzian, CLARISSA GERHÄUSER, Kira Furlano, Migle Mikutenaite, Ankita Nand, Giacomo Grillo, Jessica Heilmann, Christopher Arlidge, Evdoxia Karadoulama, Lisanne Mout, Ronald Simon, Ashish Goyal, J. Sýkora, Elisabeth L. Pezzuto, Thorsten Schlomm, Housheng Hansen He, Joachim Weischenfeldt, Guido Sauter, Christoph Plass
article en
1 citations

Abstract

Identifying drivers of cancer progression to guide treatment selection is hindered by our limited understanding of tumor heterogeneity and its impact on tumor evolution. Here, we delineate the phenotypic variability across ~300,000 cells collected from multiple tumor loci in primary prostate and matched locoregional metastases using single-cell chromatin accessibility and gene expression sequencing. We find inter-patient heterogeneity to be confined to malignant populations. Within individual tumor loci, we see phenotypic heterogeneity among malignant cell populations despite a shared clonal genotypic architecture. We also observe that malignant cell populations disseminating to locoregional lymph nodes mirror the clonal architecture and phenotypic heterogeneity across primary tumor loci, while shifting from canonical prostate-cancer states to non-canonical inflammatory-like states. Our findings suggest a bottleneck imposed during the dissemination process, funneling prostate cancer cells toward an inflammatory-like cell state. These insights into the interplay between phenotypic identity and clonal architecture refine our understanding of prostate cancer progression and suggest that convergence of cancer cells towards an inflammatory-like state underlies dissemination to lymph nodes, offering a critical framework for future studies into prostate cancer metastatic potential.

Nature CommunicationsVol. 16(1)
Ontario Institute for Cancer Research (CA), University of Copenhagen (DK), University Health Network (CA), Universität Hamburg (DE), German Cancer Research Center (DE), University of Toronto (CA), Heidelberg University (DE), Princess Margaret Cancer Centre (CA), Rigshospitalet (DK), Humboldt-Universität zu Berlin (DE), University Medical Center Hamburg-Eppendorf (DE), HCG Cancer Centre (IN), Epigenomics (Germany) (DE)
Deutsches Krebsforschungszentrum, Princess Margaret Cancer Foundation, Government of Ontario, Canadian Institutes of Health Research
Good health and well-being
Openalex Percentile: Top 20%
Single-cell and spatial transcriptomics
0.81
DOIOpen Access PDFOpenAlex
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