Castration promotes the browning of the prostate tumor microenvironment.

Publisher: BioMed Central Country of Publication: England NLM ID: 101170464 Publication Model: Electronic Cited Medium: Internet ISSN: 1478-811X (Electronic) Linking ISSN: 1478811X NLM ISO Abbreviation: Cell Commun Signal Subsets: MEDLINE

Original Publication: [London] : BioMed Central, c2003-

Prostate* ; Prostatic Neoplasms*; Male ; Humans ; Mice ; Animals ; Androgens ; Tumor Microenvironment ; Castration

Background: Adipose tissue has gained attention due to its potential paracrine role. Periprostatic adipose tissue surrounds the prostate and the prostatic urethra, and it is an essential player in prostate cancer progression. Since obesity is directly related to human tumor progression, and adipose tissue depots are one of the significant components of the tumor microenvironment, the molecular mediators of the communication between adipocytes and epithelial cells are in the spotlight. Although periprostatic white adipose tissue contributes to prostate cancer progression, brown adipose tissue (BAT), which has beneficial effects in metabolic pathologies, has been scarcely investigated concerning cancer progression. Given that adipose tissue is a target of androgen signaling, the actual role of androgen removal on the periprostatic adipose tissue was the aim of this work.
Methods: Surgical castration of the transgenic adenocarcinoma of the mouse prostate (TRAMP) was employed. By histology examination and software analysis, WAT and BAT tissue was quantified. 3T3-like adipocytes were used to study the role of Casodex® in modifying adipocyte differentiation and to investigate the function of the secretome of adipocytes on the proliferation of androgen-dependent and independent prostate cancer cells. Finally, the role of cell communication was assayed by TRAMP-C1 xenograft implanted in the presence of 3T3-like adipocytes.
Results: Androgen removal increases brown/beige adipose tissue in the fat immediately surrounding the prostate glands of TRAMP mice, concomitant with an adjustment of the metabolism. Castration increases body temperature, respiratory exchange rate, and energy expenditure. Also, in vitro, it is described that blocking androgen signaling by Casodex® increases the uncoupling protein 1 (UCP1) marker in 3T3-like adipocytes. Finally, the effect of brown/beige adipocyte secretome was studied on the proliferation of prostate cancer cells in vivo and in vitro. The secretome of brown/beige adipocytes reduces the proliferation of prostate cancer cells mediated partly by the secretion of extracellular vesicles.
Conclusions: Consequently, we concluded that hampering androgen signaling plays a crucial role in the browning of the periprostatic adipose tissue. Also, the presence of brown adipocytes exhibits the opposite effect to that of white adipocytes in vitro regulating processes that govern the mechanisms of cell proliferation of prostate cancer cells. And finally, promoting the browning of adipose tissue in the periprostatic adipose tissue might be a way to handle prostate cancer cell progression. Video Abstract.
(© 2023. BioMed Central Ltd., part of Springer Nature.)

Res Vet Sci. 1997 Mar-Apr;62(2):131-6. (PMID: 9243711)
Endocrinology. 2021 Jun 1;162(6):. (PMID: 33674833)
J Pharm Pharm Sci. 2019;22(1):418-423. (PMID: 31509504)
Int J Obes (Lond). 2022 Feb;46(2):350-358. (PMID: 34716427)
Cancers (Basel). 2021 Jul 02;13(13):. (PMID: 34283044)
Nat Rev Endocrinol. 2019 May;15(5):288-298. (PMID: 30814686)
Transl Androl Urol. 2015 Aug;4(4):455-63. (PMID: 26816843)
Front Endocrinol (Lausanne). 2021 Apr 13;12:652444. (PMID: 33927694)
Cell Metab. 2012 Mar 7;15(3):395-404. (PMID: 22405074)
Am J Clin Exp Urol. 2018 Apr 01;6(2):62-77. (PMID: 29666834)
Oncogene. 2015 Nov 26;34(48):5912-22. (PMID: 25772238)
Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):23751-23761. (PMID: 32917815)
Front Immunol. 2018 Mar 13;9:520. (PMID: 29593744)
J Cell Physiol. 2016 Dec;231(12):2664-72. (PMID: 26945682)
Prostate. 2005 Feb 15;62(3):290-8. (PMID: 15389786)
Biochim Biophys Acta. 2014 Mar;1842(3):377-92. (PMID: 23684841)
World J Oncol. 2019 Apr;10(2):63-89. (PMID: 31068988)
Diabetologia. 2019 Aug;62(8):1463-1477. (PMID: 31098671)
Crit Rev Oncol Hematol. 2022 Jan;169:103543. (PMID: 34808374)
Cancer Metab. 2017 Jan 13;5:1. (PMID: 28101337)
Biochem Biophys Res Commun. 2012 Aug 3;424(3):524-9. (PMID: 22771328)
Pharmaceutics. 2020 Apr 28;12(5):. (PMID: 32354024)
J Exp Clin Cancer Res. 2022 Jun 14;41(1):203. (PMID: 35701840)
FEBS Lett. 1984 Feb 13;167(1):10-4. (PMID: 6698197)
Endocrinology. 2010 Sep;151(9):4289-300. (PMID: 20573726)
Trends Cancer. 2018 May;4(5):374-384. (PMID: 29709261)
Cancer Res. 2023 Apr 14;83(8):1170-1172. (PMID: 37057599)
Cancer Cell. 2018 Apr 9;33(4):770-784.e6. (PMID: 29634950)
Cancer Res. 2018 Nov 15;78(22):6447-6461. (PMID: 30185551)
Sci Rep. 2018 May 21;8(1):7957. (PMID: 29785004)
Front Endocrinol (Lausanne). 2020 Mar 24;11:156. (PMID: 32265845)
Biochem Biophys Res Commun. 2016 Sep 30;478(4):1746-50. (PMID: 27608598)
Cancers (Basel). 2021 Oct 28;13(21):. (PMID: 34771580)
Front Genet. 2021 Mar 26;12:652747. (PMID: 33841508)
Prostate. 2020 Feb;80(2):162-172. (PMID: 31769890)
Nat Rev Mol Cell Biol. 2018 Apr;19(4):213-228. (PMID: 29339798)
Front Vet Sci. 2019 Nov 13;6:397. (PMID: 31799281)
Nutr Metab (Lond). 2022 Sep 6;19(1):61. (PMID: 36068578)
Prostate Cancer Prostatic Dis. 2023 Mar;26(1):5-7. (PMID: 36739329)
Br J Cancer. 2023 Apr;128(6):940-945. (PMID: 36510001)
Oncogene. 2021 Apr;40(13):2355-2366. (PMID: 33654198)
Anat Embryol (Berl). 1997 Aug;196(2):133-40. (PMID: 9278158)
Front Endocrinol (Lausanne). 2021 May 25;12:652246. (PMID: 34113316)
Prostate. 2010 Nov 1;70(15):1628-35. (PMID: 20564323)
Am J Vet Res. 2004 Dec;65(12):1708-13. (PMID: 15631038)
Compr Physiol. 2017 Sep 12;7(4):1281-1306. (PMID: 28915325)
Int J Mol Sci. 2021 May 24;22(11):. (PMID: 34074045)
Endocr Regul. 2016 Jul;50(3):137-44. (PMID: 27560796)
Int J Mol Sci. 2020 Dec 29;22(1):. (PMID: 33383677)
Cell Immunol. 2018 Aug;330:114-119. (PMID: 29526353)
Nature. 2013 Apr 25;496(7446):445-55. (PMID: 23619691)
Nature. 2022 Aug;608(7922):421-428. (PMID: 35922508)
BJU Int. 2018 May;121 Suppl 3:9-21. (PMID: 29460324)
Biol Pharm Bull. 2016;39(4):587-92. (PMID: 27040631)
Cancers (Basel). 2020 Oct 15;12(10):. (PMID: 33076397)
J Cancer. 2019 Sep 7;10(22):5608-5613. (PMID: 31632505)
J Anim Sci. 1971 May;32(5):849-58. (PMID: 5571574)
Redox Biol. 2018 Jul;17:112-127. (PMID: 29684818)
Mol Cell Endocrinol. 2011 Oct 15;345(1-2):58-67. (PMID: 21782885)
Cancer Res. 2009 Jun 15;69(12):5259-66. (PMID: 19491274)

Keywords: Adipose tissue; Browning; Prostate cancer; Tumor microenvironment; UCP1

A0Z3NAU9DP (bicalutamide)
0 (Androgens)

Date Created: 20230928 Date Completed: 20231002 Latest Revision: 20231123

20240829

PMC10536697

10.1186/s12964-023-01294-y

37770940