Distinct mesenchymal cell states mediate prostate cancer progression.

TitleDistinct mesenchymal cell states mediate prostate cancer progression.
Publication TypeJournal Article
Year of Publication2024
AuthorsPakula H, Omar M, Carelli R, Pederzoli F, Fanelli GNicolò, Pannellini T, Socciarelli F, Van Emmenis L, Rodrigues S, Fidalgo-Ribeiro C, Nuzzo PVitale, Brady NJ, Dinalankara W, Jere M, Valencia I, Saladino C, Stone J, Unkenholz C, Garner R, Alexanderani MK, Khani F, de Almeida FNunes, Abate-Shen C, Greenblatt MB, Rickman DS, Barbieri CE, Robinson BD, Marchionni L, Loda M
JournalNat Commun
Volume15
Issue1
Pagination363
Date Published2024 Jan 08
ISSN2041-1723
KeywordsAnimals, Cell Differentiation, Humans, Male, Mesenchymal Stem Cells, Mice, Prostate, Prostatic Neoplasms, Stromal Cells, Tumor Microenvironment
Abstract

In the complex tumor microenvironment (TME), mesenchymal cells are key players, yet their specific roles in prostate cancer (PCa) progression remain to be fully deciphered. This study employs single-cell RNA sequencing to delineate molecular changes in tumor stroma that influence PCa progression and metastasis. Analyzing mesenchymal cells from four genetically engineered mouse models (GEMMs) and correlating these findings with human tumors, we identify eight stromal cell populations with distinct transcriptional identities consistent across both species. Notably, stromal signatures in advanced mouse disease reflect those in human bone metastases, highlighting periostin's role in invasion and differentiation. From these insights, we derive a gene signature that predicts metastatic progression in localized disease beyond traditional Gleason scores. Our results illuminate the critical influence of stromal dynamics on PCa progression, suggesting new prognostic tools and therapeutic targets.

DOI10.1038/s41467-023-44210-1
Alternate JournalNat Commun
PubMed ID38191471
PubMed Central IDPMC10774315
Grant ListR01 CA173481 / CA / NCI NIH HHS / United States
R01 CA200859 / CA / NCI NIH HHS / United States
T32 CA260293 / CA / NCI NIH HHS / United States
P01 CA265768 / CA / NCI NIH HHS / United States
P50 CA211024 / CA / NCI NIH HHS / United States
R01 CA183929 / CA / NCI NIH HHS / United States
Related Faculty: 
Brian Robinson, M.D. David Rickman, Ph.D. Fabio Socciarelli, M.D., Ph.D. Francesca Khani, M.D. Hubert Pakula, Ph.D. Luigi Marchionni, M.D., Ph.D. Matthew B. Greenblatt, M.D., Ph.D. Massimo Loda, M.D. Mohamed Omar, MB, BCh Nicholas Brady, Ph.D. Pier Nuzzo, Ph.D.

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