Immunohistochemical Analysis of LGR5 and TROY Expression in Gastric Carcinogenesis Demonstrates an Inverse Trend
Helicobacter pylori
Wnt signaling pathway
Stem cells
Humans
Mice
Journal
Iranian biomedical journal
ISSN: 2008-823X
Titre abrégé: Iran Biomed J
Pays: Iran
ID NLM: 9814853
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
entrez:
4
12
2018
pubmed:
7
12
2018
medline:
3
5
2019
Statut:
ppublish
Résumé
Two of the Wnt signaling pathway target genes, tumor necrosis factor receptor family member (TROY) and leucine-rich G-protein coupled receptor (LGR5), are involved in the generation and maintenance of gastrointestinal epithelium. A negative modulatory role has recently been assigned to TROY, in this pathway. Here, we have examined their simultaneous expression in gastric carcinogenesis. Tumor and paired adjacent tissues of intestinal-type gastric cancer (GC) patients (n = 30) were evaluated for LGR5 and TROY expression by immunohistochemistry. The combination of the percentage of positively¬ stained cells and the intensity of staining was defined as the composite score and compared between groups. The obtained findings were re-evaluated in a mouse model. TROY expression in the tumor tissue was significantly lower than that of the adjacent tissue (2.5 ± 0.9 vs. 3.3 ± 0.9, p = 0.004), which was coincident with higher LGR5 expression (3.6 ± 1.1 vs. 2.7 ± 0.9, p = 0.001). This observation was prominent at stages II/III of GC, leading to a statistically significant mean difference of expression between these two molecules (p = 0.005). In the H. pylori infected-mouse model, this inverse expression was observed in transition from early (8-16 w) to late (26-50 w) time points, post treatment (p = 0.002). Our data demonstrates an inverse trend between TROY down-regulation and LGR5 up-regulation in GC tumors, as well as in response to H. pylori infection in mice. These findings support a potential negative modulatory role for TROY on LGR5 expression.
Sections du résumé
Background
Two of the Wnt signaling pathway target genes, tumor necrosis factor receptor family member (TROY) and leucine-rich G-protein coupled receptor (LGR5), are involved in the generation and maintenance of gastrointestinal epithelium. A negative modulatory role has recently been assigned to TROY, in this pathway. Here, we have examined their simultaneous expression in gastric carcinogenesis.
Methods
Tumor and paired adjacent tissues of intestinal-type gastric cancer (GC) patients (n = 30) were evaluated for LGR5 and TROY expression by immunohistochemistry. The combination of the percentage of positively¬ stained cells and the intensity of staining was defined as the composite score and compared between groups. The obtained findings were re-evaluated in a mouse model.
Results
TROY expression in the tumor tissue was significantly lower than that of the adjacent tissue (2.5 ± 0.9 vs. 3.3 ± 0.9, p = 0.004), which was coincident with higher LGR5 expression (3.6 ± 1.1 vs. 2.7 ± 0.9, p = 0.001). This observation was prominent at stages II/III of GC, leading to a statistically significant mean difference of expression between these two molecules (p = 0.005). In the H. pylori infected-mouse model, this inverse expression was observed in transition from early (8-16 w) to late (26-50 w) time points, post treatment (p = 0.002).
Conclusion
Our data demonstrates an inverse trend between TROY down-regulation and LGR5 up-regulation in GC tumors, as well as in response to H. pylori infection in mice. These findings support a potential negative modulatory role for TROY on LGR5 expression.
Substances chimiques
Biomarkers, Tumor
0
LGR5 protein, human
0
Receptors, G-Protein-Coupled
0
Receptors, Tumor Necrosis Factor
0
TNFRSF19 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
107-20Références
J Clin Pathol. 2005 May;58(5):515-9
pubmed: 15858124
Gastroenterol Clin North Am. 2013 Jun;42(2):211-7
pubmed: 23639637
Nature. 2011 Jul 04;476(7360):293-7
pubmed: 21727895
Ann Surg Oncol. 2011 Apr;18(4):1166-74
pubmed: 21125339
Nat Cell Biol. 2010 Mar;12(3):299-305
pubmed: 20154679
Cancer Res. 2002 Jun 15;62(12):3503-6
pubmed: 12067995
Am J Cancer Res. 2017 May 01;7(5):1016-1036
pubmed: 28560055
J Gastroenterol. 2011 Jul;46(7):855-65
pubmed: 21626457
Asian Pac J Cancer Prev. 2018 Mar 27;19(3):591-603
pubmed: 29579788
Dis Esophagus. 2010 Feb;23(2):168-74
pubmed: 19549212
Cell. 2008 Feb 22;132(4):598-611
pubmed: 18295578
Appl Immunohistochem Mol Morphol. 2019 Apr;27(4):270-277
pubmed: 29084052
Gut. 2005 Jun;54(6):764-8
pubmed: 15888780
Int J Cancer. 2015 Mar 1;136(5):E359-86
pubmed: 25220842
Gut. 1994 Jun;35(6):758-63
pubmed: 8020800
Saudi Med J. 2011 Nov;32(11):1202-3
pubmed: 22057614
Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5186-91
pubmed: 15795379
PLoS One. 2012;7(4):e35486
pubmed: 22530031
Indian J Med Microbiol. 2008 Apr-Jun;26(2):127-31
pubmed: 18445947
Proc Natl Acad Sci U S A. 2011 May 31;108(22):9238-43
pubmed: 21562218
Hepatology. 2003 Mar;37(3):528-33
pubmed: 12601349
World J Gastroenterol. 2013 Dec 14;19(46):8714-21
pubmed: 24379591
Jpn J Cancer Res. 2002 Oct;93(10):1083-9
pubmed: 12417037
Science. 2003 May 30;300(5624):1430-4
pubmed: 12775840
Br J Cancer. 2014 Apr 15;110(8):2011-20
pubmed: 24594994
Oncotarget. 2016 Jul 18;8(31):50557-50569
pubmed: 28881583
Cancer. 1992 Jul 1;70(1):50-5
pubmed: 1606546
Mol Cancer Res. 2010 Nov;8(11):1558-67
pubmed: 20881009
Science. 2014 Oct 3;346(6205):1248012
pubmed: 25278615
Cell. 2017 May 4;169(4):636-650.e14
pubmed: 28434617
Front Biosci (Schol Ed). 2013 Jan 01;5:720-31
pubmed: 23277081
J Biol Chem. 2010 May 7;285(19):14438-49
pubmed: 20223822
Nat Rev Cancer. 2018 Mar;18(3):187-201
pubmed: 29348578
Genome Biol. 2014 Mar 21;15(3):R52
pubmed: 24655370
Cancer. 1997 Nov 1;80(9):1803-4
pubmed: 9351551
Iran Biomed J. 2015;19(3):133-42
pubmed: 26117138
J Med Screen. 2004;11(3):141-7
pubmed: 15333273
Gastroenterology. 2013 Feb;144(2):381-91
pubmed: 23142137
Adv Exp Med Biol. 1995;362:139-43
pubmed: 8540312
Oncol Lett. 2018 Apr;15(4):5989-5994
pubmed: 29556315
Int J Cancer. 2007 Mar 15;120(6):1304-10
pubmed: 17187358
Oncol Rep. 2014 Jul;32(1):181-8
pubmed: 24859092
Gastric Cancer. 2018 Mar;21(2):196-203
pubmed: 28725964
Cancer Biomark. 2017 Dec 6;20(4):563-573
pubmed: 28946555
Nature. 2007 Oct 25;449(7165):1003-7
pubmed: 17934449
Dig Dis Sci. 2013 Jan;58(1):140-9
pubmed: 22945475
Science. 2002 Jan 25;295(5555):683-6
pubmed: 11743164
World J Gastrointest Pathophysiol. 2014 Aug 15;5(3):366-72
pubmed: 25133037
Nature. 2005 Apr 14;434(7035):843-50
pubmed: 15829953
CA Cancer J Clin. 2015 Mar;65(2):87-108
pubmed: 25651787
Oncotarget. 2017 Jun 28;8(38):63382-63391
pubmed: 28968998
Chin J Cancer Res. 2013 Feb;25(1):79-89
pubmed: 23372345
Curr Microbiol. 2010 Apr;60(4):254-62
pubmed: 19949795
Asian Pac J Cancer Prev. 2015;16(10):4177-83
pubmed: 26028069
Int J Cancer. 2014 Oct 15;135(8):1800-11
pubmed: 24623448
Mol Med Rep. 2012 May;5(5):1191-6
pubmed: 22367735
Gastroenterology. 2015 Jun;148(7):1392-404.e21
pubmed: 25725293
Gene. 2013 Aug 1;525(1):18-25
pubmed: 23664892
Front Immunol. 2014 Jul 22;5:347
pubmed: 25101088
J Cancer Prev. 2016 Dec;21(4):279-287
pubmed: 28053963
ScientificWorldJournal. 2008 Nov 23;8:1168-76
pubmed: 19030762
Oncotarget. 2016 Sep 20;7(38):62049-62069
pubmed: 27557490
Gut. 1999 May;44(5):693-7
pubmed: 10205207