دورية أكاديمية
Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer.
العنوان: | Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer. |
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المؤلفون: | Al-Nakouzi N; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada. nalnakouzi@prostatecentre.com.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada. nalnakouzi@prostatecentre.com., Wang CK; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Oo HZ; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Nelepcu I; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Lallous N; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Spliid CB; Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA., Khazamipour N; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Lo J; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Truong S; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Collins C; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Hui D; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Esfandnia S; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Adomat H; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Clausen TM; Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA., Gustavsson T; Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, Copenhagen, Denmark.; VAR2pharmaceuticals Ole Maaløes Vej 3, 2200, København, Denmark., Choudhary S; Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, Copenhagen, Denmark.; VAR2pharmaceuticals Ole Maaløes Vej 3, 2200, København, Denmark., Dagil R; Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, Copenhagen, Denmark.; VAR2pharmaceuticals Ole Maaløes Vej 3, 2200, København, Denmark., Corey E; Department of Urology, University of Washington, Seattle, WA, 98195, USA., Wang Y; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Chauchereau A; Prostate Cancer Group, INSERM UMR981, Gustave Roussy, University of Paris-Saclay, F-94805, Villejuif, France., Fazli L; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Esko JD; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA., Salanti A; Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, Copenhagen, Denmark., Nelson PS; Department of Urology, University of Washington, Seattle, WA, 98195, USA.; Fred Hutchinson Cancer Centre, Seattle, WA, 98109-1024, USA., Gleave ME; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada., Daugaard M; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada. mads.daugaard@ubc.ca.; Vancouver Prostate Centre, Vancouver, BC, V6H 3Z6, Canada. mads.daugaard@ubc.ca. |
المصدر: | Nature communications [Nat Commun] 2022 Aug 13; Vol. 13 (1), pp. 4760. Date of Electronic Publication: 2022 Aug 13. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Prostatic Neoplasms, Castration-Resistant*/drug therapy, Androgens ; Chondroitin Sulfates ; Glycocalyx/metabolism ; Humans ; Male ; Signal Transduction ; Tumor Microenvironment |
مستخلص: | Lineage plasticity of prostate cancer is associated with resistance to androgen receptor (AR) pathway inhibition (ARPI) and supported by a reactive tumor microenvironment. Here we show that changes in chondroitin sulfate (CS), a major glycosaminoglycan component of the tumor cell glycocalyx and extracellular matrix, is AR-regulated and promotes the adaptive progression of castration-resistant prostate cancer (CRPC) after ARPI. AR directly represses transcription of the 4-O-sulfotransferase gene CHST11 under basal androgen conditions, maintaining steady-state CS in prostate adenocarcinomas. When AR signaling is inhibited by ARPI or lost during progression to non-AR-driven CRPC as a consequence of lineage plasticity, CHST11 expression is unleashed, leading to elevated 4-O-sulfated chondroitin levels. Inhibition of the tumor cell CS glycocalyx delays CRPC progression, and impairs growth and motility of prostate cancer after ARPI. Thus, a reactive CS glycocalyx supports adaptive survival and treatment resistance after ARPI, representing a therapeutic opportunity in patients with advanced prostate cancer. (© 2022. The Author(s).) |
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معلومات مُعتمدة: | P50 CA097186 United States CA NCI NIH HHS; PJT-153092 Canada CIHR |
المشرفين على المادة: | 0 (Androgens) 9007-28-7 (Chondroitin Sulfates) |
تواريخ الأحداث: | Date Created: 20220813 Date Completed: 20220816 Latest Revision: 20220908 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC9376089 |
DOI: | 10.1038/s41467-022-32530-7 |
PMID: | 35963852 |
قاعدة البيانات: | MEDLINE |
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