Paracrine Wnt signaling is necessary for prostate epithelial proliferation.
Wls
Wnt
homeostasis
prostate cancer
prostate stromal cells
Journal
The Prostate
ISSN: 1097-0045
Titre abrégé: Prostate
Pays: United States
ID NLM: 8101368
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
18
12
2021
received:
08
11
2021
accepted:
21
12
2021
pubmed:
12
1
2022
medline:
15
4
2022
entrez:
11
1
2022
Statut:
ppublish
Résumé
The Wnt proteins play key roles in the development, homeostasis, and disease progression of many organs including the prostate. However, the spatiotemporal expression patterns of Wnt proteins in prostate cell lineages at different developmental stages and in prostate cancer remain inadequately characterized. We isolated the epithelial and stromal cells in the developing and mature mouse prostate by flow cytometry and determined the expression levels of Wnt ligands. We used Visium spatial gene expression analysis to determine the spatial distribution of Wnt ligands in the mouse prostatic glands. Using laser-capture microscopy in combination with gene expression analysis, we also determined the expression patterns of Wnt signaling components in stromal and cancer cells in advanced human prostate cancer specimens. To investigate how the stroma-derived Wnt ligands affect prostate development and homeostasis, we used a Col1a2-CreER We showed that the prostate stromal cells are a major source of several Wnt ligands. Visium spatial gene expression analysis revealed a distinct spatial distribution of Wnt ligands in the prostatic glands. We also showed that Wnt signaling components are highly expressed in the stromal compartment of primary and advanced human prostate cancer. Blocking stromal Wnt secretion attenuated prostate epithelial proliferation and regeneration but did not affect cell survival and lineage maintenance. Our study demonstrates a critical role of stroma-derived Wnt ligands in prostate development and homeostasis.
Identifiants
pubmed: 35014711
doi: 10.1002/pros.24298
pmc: PMC8866211
mid: NIHMS1767723
doi:
Substances chimiques
Ligands
0
Wnt Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
517-530Subventions
Organisme : NCI NIH HHS
ID : P50 CA097186
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA234715
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK092202
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107436
Pays : United States
Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
J Pathol. 2021 Oct;255(2):141-154
pubmed: 34173975
Cancer Res. 2004 Nov 1;64(21):7918-26
pubmed: 15520198
Differentiation. 2008 Jul;76(6):641-59
pubmed: 18462433
Science. 2014 Oct 3;346(6205):1248012
pubmed: 25278615
Stem Cells. 2016 Jan;34(1):191-202
pubmed: 26418304
iScience. 2019 Mar 29;13:328-338
pubmed: 30878879
Cell. 2015 May 21;161(5):1215-1228
pubmed: 26000489
Adv Exp Med Biol. 2019;1210:67-86
pubmed: 31900905
Cancer Cell. 2012 Feb 14;21(2):253-65
pubmed: 22340597
Differentiation. 2003 Sep;71(7):402-13
pubmed: 12969333
Nat Rev Urol. 2012 Aug;9(8):418-28
pubmed: 22710668
Stem Cells. 2011 Apr;29(4):678-88
pubmed: 21308863
Nat Med. 2012 Sep;18(9):1359-68
pubmed: 22863786
Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11896-903
pubmed: 12909713
Cold Spring Harb Perspect Med. 2018 May 1;8(5):
pubmed: 29038334
Oncogene. 2011 Apr 21;30(16):1868-79
pubmed: 21151173
Exp Ther Med. 2016 Apr;11(4):1361-1366
pubmed: 27073450
Prostate. 2014 Nov;74(15):1506-20
pubmed: 25175604
Cell Stem Cell. 2019 May 2;24(5):753-768.e6
pubmed: 30982770
Cell. 2006 May 5;125(3):509-22
pubmed: 16678095
Anat Rec. 1973 Jan;175(1):87-96
pubmed: 4734188
Endocrinology. 2016 May;157(5):2116-28
pubmed: 26963473
PLoS One. 2008 May 14;3(5):e2186
pubmed: 18478098
Science. 2015 Sep 18;349(6254):1351-6
pubmed: 26383955
Mol Cancer Res. 2013 May;11(5):482-93
pubmed: 23386686
Cell Stem Cell. 2012 Nov 2;11(5):676-88
pubmed: 23122291
PLoS Genet. 2013;9(1):e1003180
pubmed: 23300485
Biol Reprod. 2018 Oct 1;99(4):806-816
pubmed: 29767687
Oncogene. 2021 Jan;40(1):203-214
pubmed: 33110232
Cell. 2014 Sep 25;159(1):163-175
pubmed: 25201529
Dev Biol. 2009 Apr 15;328(2):188-99
pubmed: 19389372
Dev Biol. 2012 Nov 15;371(2):246-55
pubmed: 22960283
Dev Biol. 2003 Jan 15;253(2):165-74
pubmed: 12645922
Prostate. 2019 Oct;79(14):1692-1704
pubmed: 31433503
Genes Dev. 2000 Oct 1;14(19):2410-34
pubmed: 11018010
Dev Biol. 2008 Dec 1;324(1):10-7
pubmed: 18804104
Mol Endocrinol. 1992 Dec;6(12):2123-8
pubmed: 1491693
Stem Cells. 2020 Nov;38(11):1479-1491
pubmed: 32627901
Mol Cell Endocrinol. 2017 Jan 5;439:26-34
pubmed: 27769713
Dev Dyn. 2011 Nov;240(11):2548-60
pubmed: 21936019
Prostate. 2009 Feb 15;69(3):249-62
pubmed: 18991257
Cell. 2017 Jun 1;169(6):985-999
pubmed: 28575679