Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal Tissue

Lgr5 has recently been identified as a murine marker of intestinal stem cells. Its expression has not been well characterized in human gastrointestinal tissues, but has been reported in certain cancers. With the increasing appreciation for the role of cancer stem cells or tumor-initiating cells in c...

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Main Authors: Laren Becker, Qin Huang, Hiroshi Mashimo
Format: Article
Language:English
Published: Wiley 2008-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1100/tsw.2008.148
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author Laren Becker
Qin Huang
Hiroshi Mashimo
author_facet Laren Becker
Qin Huang
Hiroshi Mashimo
author_sort Laren Becker
collection DOAJ
description Lgr5 has recently been identified as a murine marker of intestinal stem cells. Its expression has not been well characterized in human gastrointestinal tissues, but has been reported in certain cancers. With the increasing appreciation for the role of cancer stem cells or tumor-initiating cells in certain tumors, we sought to explore the expression of Lgr5 in normal and premalignant human gastrointestinal tissues. Using standard immunostaining, we compared expression of Lgr5 in normal colon and small intestine vs. small intestinal and colonic adenomas and Barrett's esophagus. In the normal tissue, Lgr5 was expressed in the expected stem cell niche, at the base of crypts, as seen in mice. However, in premalignant lesions, Lgr5+ cells were not restricted to the crypt base. Additionally, their overall numbers were increased. In colonic adenomas, Lgr5+ cells were commonly found clustered at the luminal surface and rarely at the crypt base. Finally, we compared immunostaining of Lgr5 with that of CD133, a previously characterized marker for tumor-initiating cells in colon cancer, and found that they identified distinct subpopulations of cells that were in close proximity, but did not costain. Our findings suggest that (1) Lgr5 is a potential marker of intestinal stem cells in humans and (2) loss of restriction to the stem cell niche is an early event in the premalignant transformation of stem cells and may play a role in carcinogenesis.
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spelling doaj-art-c32d07703ab244f8992cff7dbc7a88f32025-02-03T07:23:55ZengWileyThe Scientific World Journal1537-744X2008-01-0181168117610.1100/tsw.2008.148Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal TissueLaren Becker0Qin Huang1Hiroshi Mashimo2Beth Israel Deaconess Medical Center, Boston, London, UKVA Boston Healthcare System, Boston, London, UKVA Boston Healthcare System, Boston, London, UKLgr5 has recently been identified as a murine marker of intestinal stem cells. Its expression has not been well characterized in human gastrointestinal tissues, but has been reported in certain cancers. With the increasing appreciation for the role of cancer stem cells or tumor-initiating cells in certain tumors, we sought to explore the expression of Lgr5 in normal and premalignant human gastrointestinal tissues. Using standard immunostaining, we compared expression of Lgr5 in normal colon and small intestine vs. small intestinal and colonic adenomas and Barrett's esophagus. In the normal tissue, Lgr5 was expressed in the expected stem cell niche, at the base of crypts, as seen in mice. However, in premalignant lesions, Lgr5+ cells were not restricted to the crypt base. Additionally, their overall numbers were increased. In colonic adenomas, Lgr5+ cells were commonly found clustered at the luminal surface and rarely at the crypt base. Finally, we compared immunostaining of Lgr5 with that of CD133, a previously characterized marker for tumor-initiating cells in colon cancer, and found that they identified distinct subpopulations of cells that were in close proximity, but did not costain. Our findings suggest that (1) Lgr5 is a potential marker of intestinal stem cells in humans and (2) loss of restriction to the stem cell niche is an early event in the premalignant transformation of stem cells and may play a role in carcinogenesis.http://dx.doi.org/10.1100/tsw.2008.148
spellingShingle Laren Becker
Qin Huang
Hiroshi Mashimo
Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal Tissue
The Scientific World Journal
title Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal Tissue
title_full Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal Tissue
title_fullStr Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal Tissue
title_full_unstemmed Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal Tissue
title_short Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal Tissue
title_sort immunostaining of lgr5 an intestinal stem cell marker in normal and premalignant human gastrointestinal tissue
url http://dx.doi.org/10.1100/tsw.2008.148
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AT qinhuang immunostainingoflgr5anintestinalstemcellmarkerinnormalandpremalignanthumangastrointestinaltissue
AT hiroshimashimo immunostainingoflgr5anintestinalstemcellmarkerinnormalandpremalignanthumangastrointestinaltissue