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Objective: To elucidate the regulation, function of the chemokine CXC-motif ligand 12 (CXCL12) and its receptors (CXCR) 4 and 7 in prostate cancer tumor microenvironment.

Material: In-silico-analysis of expression in prostate cancer tissues. In-vitro comparison, testing of regulation in human prostate cancer cells LNCaP, DU145, and PC3.

Treatment: Dihydrotestosterone (DHT) treatments (0-10 nM) were for 0-48 h. The inflammatory agent Flagellin treatment (20 ng/ml) was for 2 h. Migration assays were performed for 24 h using 10 ng/ml CXCL12.

Methods: Real-time PCR, western analysis, and migration assays were used to determine mRNA, protein, and functional changes, respectively.

Results: Malignant prostate cancer tissues exhibit higher CXCR4/7 mRNA ratio, and higher CXCR7 mRNA levels were detected in the androgen-responsive LNCaP cells. Putative androgen-responsive elements were identified in CXCR4, 7 gene, and exposure to DHT, flagellin increased CXCR4 mRNA but decreased CXCR7 mRNA levels in LNCaP cells. Androgen receptor siRNA significantly attenuated the effects of DHT on CXCR4, 7 mRNA in LNCaP cells. However, DHT and flagellin only decrease CXCR7 protein and additively increased migration of LNCaP cells towards CXCL12.

Conclusions: Down regulation of CXCR7 protein by DHT and flagellin increased migration, supporting CXCR7 as decoy receptor counteracting CXCL12/CXCR4-mediated migration in prostate cancer cells.

Titel:	Modulation of CXC-motif chemokine receptor 7, but not 4, expression is related to migration of the human prostate cancer cell LNCaP: regulation by androgen and inflammatory stimuli.
Autor/in / Beteiligte Person:	Yu, L ; Pham, Q ; Yu, LL ; Wang, TTY
Link:	View record at Springer (Volltext)
Zeitschrift:	Inflammation research : official journal of the European Histamine Research Society ... [et al.], Jg. 69 (2020-02-01), Heft 2, S. 167-178
Veröffentlichung:	Basel, Switzerland : Birkhäuser, c1995-, 2020
Medientyp:	academicJournal
ISSN:	1420-908X (electronic)
DOI:	10.1007/s00011-019-01305-0
Schlagwort:	Cell Line, Tumor Cell Movement Chemokine CXCL12 biosynthesis Chemokine CXCL12 genetics Computer Simulation Dihydrotestosterone pharmacology Flagellin pharmacology Humans Male Prostatic Neoplasms pathology RNA, Messenger biosynthesis RNA, Neoplasm biosynthesis Receptors, Androgen biosynthesis Receptors, Androgen genetics Receptors, CXCR biosynthesis Receptors, CXCR4 biosynthesis Tumor Microenvironment Androgens metabolism Inflammation metabolism Prostatic Neoplasms genetics Receptors, CXCR genetics Receptors, CXCR4 genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Inflamm Res] 2020 Feb; Vol. 69 (2), pp. 167-178. <i>Date of Electronic Publication: </i>2019 Dec 21. MeSH Terms: Androgens / metabolism ; Inflammation / metabolism ; Prostatic Neoplasms / genetics ; Receptors, CXCR / genetics ; Receptors, CXCR4 / *genetics ; Cell Line, Tumor ; Cell Movement ; Chemokine CXCL12 / biosynthesis ; Chemokine CXCL12 / genetics ; Computer Simulation ; Dihydrotestosterone / pharmacology ; Flagellin / pharmacology ; Humans ; Male ; Prostatic Neoplasms / pathology ; RNA, Messenger / biosynthesis ; RNA, Neoplasm / biosynthesis ; Receptors, Androgen / biosynthesis ; Receptors, Androgen / genetics ; Receptors, CXCR / biosynthesis ; Receptors, CXCR4 / biosynthesis ; Tumor Microenvironment References: Brawley OW. Prostate cancer epidemiology in the United States. World J Urol. 2012;30:195–200. 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(PMID: 10.1093/carcin/bgh317) Grant Information: 8040-51530-056-00D Agricultural Research Service Contributed Indexing: Keywords: CXCR4; CXCR7; Chemokine; DHT; Migration; Prostate cancer Substance Nomenclature: 0 (ACKR3 protein, human) ; 0 (Androgens) ; 0 (CXCL12 protein, human) ; 0 (CXCR4 protein, human) ; 0 (Chemokine CXCL12) ; 0 (RNA, Messenger) ; 0 (RNA, Neoplasm) ; 0 (Receptors, Androgen) ; 0 (Receptors, CXCR) ; 0 (Receptors, CXCR4) ; 08J2K08A3Y (Dihydrotestosterone) ; 12777-81-0 (Flagellin) Entry Date(s): Date Created: 20191223 Date Completed: 20201120 Latest Revision: 20221019 Update Code: 20231215

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Modulation of CXC-motif chemokine receptor 7, but not 4, expression is related to migration of the human prostate cancer cell LNCaP: regulation by androgen and inflammatory stimuli.