Distinct mesenchymal cell states mediate prostate cancer progression.

التفاصيل البيبلوغرافية
العنوان: Distinct mesenchymal cell states mediate prostate cancer progression.
المؤلفون: Pakula H; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Omar M; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Carelli R; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Pederzoli F; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Fanelli GN; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA.; Department of Laboratory Medicine, Pisa University Hospital, Division of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56126, Italy., Pannellini T; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Van Emmenis L; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Rodrigues S; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Fidalgo-Ribeiro C; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Nuzzo PV; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Brady NJ; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Jere M; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Unkenholz C; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Alexanderani MK; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Khani F; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA.; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, Belfer Research Building, 413 East 69th Street, New York, NY 10021, USA.; Department of Urology, Weill Cornell Medicine, New York, NY 10021, USA., de Almeida FN; Departments of Molecular Pharmacology and Therapeutics, Urology, Medicine, Pathology & Cell Biology and Systems Biology, Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA., Abate-Shen C; Departments of Molecular Pharmacology and Therapeutics, Urology, Medicine, Pathology & Cell Biology and Systems Biology, Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA., Greenblatt MB; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Rickman DS; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Barbieri CE; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA.; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, Belfer Research Building, 413 East 69th Street, New York, NY 10021, USA.; Department of Urology, Weill Cornell Medicine, New York, NY 10021, USA., Robinson BD; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA.; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, Belfer Research Building, 413 East 69th Street, New York, NY 10021, USA.; Department of Urology, Weill Cornell Medicine, New York, NY 10021, USA., Marchionni L; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA., Loda M; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10021, USA.; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, Belfer Research Building, 413 East 69th Street, New York, NY 10021, USA.; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2023 Apr 01. Date of Electronic Publication: 2023 Apr 01.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: Alterations in tumor stroma influence prostate cancer progression and metastatic potential. However, the molecular underpinnings of this stromal-epithelial crosstalk are largely unknown. Here, we compare mesenchymal cells from four genetically engineered mouse models (GEMMs) of prostate cancer representing different stages of the disease to their wild-type (WT) counterparts by single-cell RNA sequencing (scRNA-seq) and, ultimately, to human tumors with comparable genotypes. We identified 8 transcriptionally and functionally distinct stromal populations responsible for common and GEMM-specific transcriptional programs. We show that stromal responses are conserved in mouse models and human prostate cancers with the same genomic alterations. We noted striking similarities between the transcriptional profiles of the stroma of murine models of advanced disease and those of of human prostate cancer bone metastases. These profiles were then used to build a robust gene signature that can predict metastatic progression in prostate cancer patients with localized disease and is also associated with progression-free survival independent of Gleason score. Taken together, this offers new evidence that stromal microenvironment mediates prostate cancer progression, further identifying tissue-based biomarkers and potential therapeutic targets of aggressive and metastatic disease.
Competing Interests: Ethics declarations The authors declare no competing interests.
التعليقات: Update in: Nat Commun. 2024 Jan 8;15(1):363. (PMID: 38191471)
معلومات مُعتمدة: R01 CA173481 United States CA NCI NIH HHS; R01 CA200859 United States CA NCI NIH HHS; T32 CA260293 United States CA NCI NIH HHS; P01 CA265768 United States CA NCI NIH HHS; P50 CA211024 United States CA NCI NIH HHS; R01 CA183929 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Wnt signaling; bone metastasis; cancer-associated fibroblasts; complement protein; genetically-engineered mouse models; innate and adaptive immunity; neuroendocrine tumor stroma; predictive and prognostic signatures; prostate cancer; single-cell RNA sequencing; tumor microenvironment
تواريخ الأحداث: Date Created: 20230410 Latest Revision: 20240122
رمز التحديث: 20240122
مُعرف محوري في PubMed: PMC10081210
DOI: 10.1101/2023.03.29.534769
PMID: 37034687
قاعدة البيانات: MEDLINE
الوصف
DOI:10.1101/2023.03.29.534769