The spatial distribution of LGR5+ cells correlates with gastric cancer progression.

In this study we tested the prevalence, histoanatomical distribution and tumour biological significance of the Wnt target protein and cancer stem cell marker LGR5 in tumours of the human gastrointestinal tract. Differential expression of LGR5 was studied on transcriptional (real-time polymerase chai...

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Autores principales:	Eva Simon, Diana Petke, Christine Böger, Hans-Michael Behrens, Viktoria Warneke, Matthias Ebert, Christoph Röcken
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ff1300d5bbd40f8a33311cea85fb1c1
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spelling	oai:doaj.org-article:3ff1300d5bbd40f8a33311cea85fb1c12021-11-18T07:21:44ZThe spatial distribution of LGR5+ cells correlates with gastric cancer progression.1932-620310.1371/journal.pone.0035486https://doaj.org/article/3ff1300d5bbd40f8a33311cea85fb1c12012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22530031/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203In this study we tested the prevalence, histoanatomical distribution and tumour biological significance of the Wnt target protein and cancer stem cell marker LGR5 in tumours of the human gastrointestinal tract. Differential expression of LGR5 was studied on transcriptional (real-time polymerase chain reaction) and translational level (immunohistochemistry) in malignant and corresponding non-malignant tissues of 127 patients comprising six different primary tumour sites, i.e. oesophagus, stomach, liver, pancreas, colon and rectum. The clinico-pathological significance of LGR5 expression was studied in 100 patients with gastric carcinoma (GC). Non-neoplastic tissue usually harboured only very few scattered LGR5(+) cells. The corresponding carcinomas of the oesophagus, stomach, liver, pancreas, colon and rectum showed significantly more LGR5(+) cells as well as significantly higher levels of LGR5-mRNA compared with the corresponding non-neoplastic tissue. Double staining experiments revealed a coexpression of LGR5 with the putative stem cell markers CD44, Musashi-1 and ADAM17. Next we tested the hypothesis that the sequential changes of gastric carcinogenesis, i.e. chronic atrophic gastritis, intestinal metaplasia and invasive carcinoma, are associated with a reallocation of the LGR5(+) cells. Interestingly, the spatial distribution of LGR5 changed: in non-neoplastic stomach mucosa, LGR5(+) cells were found predominantly in the mucous neck region; in intestinal metaplasia LGR5(+) cells were localized at the crypt base, and in GC LGR5(+) cells were present at the luminal surface, the tumour centre and the invasion front. The expression of LGR5 in the tumour centre and invasion front of GC correlated significantly with the local tumour growth (T-category) and the nodal spread (N-category). Furthermore, patients with LGR5(+) GCs had a shorter median survival (28.0±8.6 months) than patients with LGR5(-) GCs (54.5±6.3 months). Our results show that LGR5 is differentially expressed in gastrointestinal cancers and that the spatial histoanatomical distribution of LGR5(+) cells has to be considered when their tumour biological significance is sought.Eva SimonDiana PetkeChristine BögerHans-Michael BehrensViktoria WarnekeMatthias EbertChristoph RöckenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35486 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eva Simon Diana Petke Christine Böger Hans-Michael Behrens Viktoria Warneke Matthias Ebert Christoph Röcken The spatial distribution of LGR5+ cells correlates with gastric cancer progression.
description	In this study we tested the prevalence, histoanatomical distribution and tumour biological significance of the Wnt target protein and cancer stem cell marker LGR5 in tumours of the human gastrointestinal tract. Differential expression of LGR5 was studied on transcriptional (real-time polymerase chain reaction) and translational level (immunohistochemistry) in malignant and corresponding non-malignant tissues of 127 patients comprising six different primary tumour sites, i.e. oesophagus, stomach, liver, pancreas, colon and rectum. The clinico-pathological significance of LGR5 expression was studied in 100 patients with gastric carcinoma (GC). Non-neoplastic tissue usually harboured only very few scattered LGR5(+) cells. The corresponding carcinomas of the oesophagus, stomach, liver, pancreas, colon and rectum showed significantly more LGR5(+) cells as well as significantly higher levels of LGR5-mRNA compared with the corresponding non-neoplastic tissue. Double staining experiments revealed a coexpression of LGR5 with the putative stem cell markers CD44, Musashi-1 and ADAM17. Next we tested the hypothesis that the sequential changes of gastric carcinogenesis, i.e. chronic atrophic gastritis, intestinal metaplasia and invasive carcinoma, are associated with a reallocation of the LGR5(+) cells. Interestingly, the spatial distribution of LGR5 changed: in non-neoplastic stomach mucosa, LGR5(+) cells were found predominantly in the mucous neck region; in intestinal metaplasia LGR5(+) cells were localized at the crypt base, and in GC LGR5(+) cells were present at the luminal surface, the tumour centre and the invasion front. The expression of LGR5 in the tumour centre and invasion front of GC correlated significantly with the local tumour growth (T-category) and the nodal spread (N-category). Furthermore, patients with LGR5(+) GCs had a shorter median survival (28.0±8.6 months) than patients with LGR5(-) GCs (54.5±6.3 months). Our results show that LGR5 is differentially expressed in gastrointestinal cancers and that the spatial histoanatomical distribution of LGR5(+) cells has to be considered when their tumour biological significance is sought.
format	article
author	Eva Simon Diana Petke Christine Böger Hans-Michael Behrens Viktoria Warneke Matthias Ebert Christoph Röcken
author_facet	Eva Simon Diana Petke Christine Böger Hans-Michael Behrens Viktoria Warneke Matthias Ebert Christoph Röcken
author_sort	Eva Simon
title	The spatial distribution of LGR5+ cells correlates with gastric cancer progression.
title_short	The spatial distribution of LGR5+ cells correlates with gastric cancer progression.
title_full	The spatial distribution of LGR5+ cells correlates with gastric cancer progression.
title_fullStr	The spatial distribution of LGR5+ cells correlates with gastric cancer progression.
title_full_unstemmed	The spatial distribution of LGR5+ cells correlates with gastric cancer progression.
title_sort	spatial distribution of lgr5+ cells correlates with gastric cancer progression.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/3ff1300d5bbd40f8a33311cea85fb1c1
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The spatial distribution of LGR5+ cells correlates with gastric cancer progression.

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