Edi Levi1, Paula Sochacki1, Nabiha Khoury1, Bhaumik B Patel1, Adhip Pn Majumdar1. 1. Edi Levi, Paula Sochacki, Nabiha Khoury, Bhaumik B Patel, Adhip PN Majumdar, Department of Veterans Affairs, John D Dingell VA Medical Center, Wayne State University, Detroit, MI 48201, United States.
Abstract
AIM: To demonstrated the combined effects of aging and carcinogen treatment on cancer stem/stem-like cells (CSCs) of gastric mucosa in an animal model. METHODS: In this study we investigated the effects of aging and Helicobacter pylori (H. pylori) inflammation as a model for inflammation induced carcinogenesis in human and rat gastric mucosa samples. In aging studies, we compared 4-mo old (young) with 22 mo (aged) old Fischer-344 rats. For human studies, gastric biopsies and resection specimens representing normal mucosa or different stages of H. pylori gastritis and gastric adenocarcinomas were used for determining the expression of stem cell markers CD166, ALDH1 and LGR5. In addition we performed immunofluorescent double labeling for B-catenin and Lgr5 in both rat and human gastric tissues to examine the status of Wnt signaling in these cells. RESULTS: CSC markers ALDH1, LGR5, and CD166 were expressed in very low levels in normal human gastric mucosa or young rat gastric mucosa. In contrast, level of expression for all three markers significantly increased in H. pylori gastritis and gastric adenocarcinomas as well as in normal gastric mucosa in aged rats. We also observed cytoplasmic B-catenin staining in both aged rat and human H. pylori inflamed gastric mucosa, which were found to be colocalized with Lgr5 immunoreactive cells. The increased number of ALDH1, CD166 and LGR5 positive cells in H. pylori gastritis indicates that increased number of stem-like cells in gastric mucosa is an early event, and may constitute an important step in the progression to neoplasia. CONCLUSION: Our observation of the age-related increase in cancer stem/stem-like cells in the gastric mucosa may explain the increased incidence of gastric cancer during aging. Combination of aging and H. pylori infection may have additive effects in progression to neoplasia.
AIM: To demonstrated the combined effects of aging and carcinogen treatment on cancer stem/stem-like cells (CSCs) of gastric mucosa in an animal model. METHODS: In this study we investigated the effects of aging and Helicobacter pylori (H. pylori) inflammation as a model for inflammation induced carcinogenesis in human and rat gastric mucosa samples. In aging studies, we compared 4-mo old (young) with 22 mo (aged) old Fischer-344 rats. For human studies, gastric biopsies and resection specimens representing normal mucosa or different stages of H. pylorigastritis and gastric adenocarcinomas were used for determining the expression of stem cell markers CD166, ALDH1 and LGR5. In addition we performed immunofluorescent double labeling for B-catenin and Lgr5 in both rat and human gastric tissues to examine the status of Wnt signaling in these cells. RESULTS: CSC markers ALDH1, LGR5, and CD166 were expressed in very low levels in normal human gastric mucosa or young rat gastric mucosa. In contrast, level of expression for all three markers significantly increased in H. pylorigastritis and gastric adenocarcinomas as well as in normal gastric mucosa in aged rats. We also observed cytoplasmic B-catenin staining in both aged rat and humanH. pylori inflamed gastric mucosa, which were found to be colocalized with Lgr5 immunoreactive cells. The increased number of ALDH1, CD166 and LGR5 positive cells in H. pylorigastritis indicates that increased number of stem-like cells in gastric mucosa is an early event, and may constitute an important step in the progression to neoplasia. CONCLUSION: Our observation of the age-related increase in cancer stem/stem-like cells in the gastric mucosa may explain the increased incidence of gastric cancer during aging. Combination of aging and H. pyloriinfection may have additive effects in progression to neoplasia.
Authors: Jung D Oh; Helene Kling-Bäckhed; Marios Giannakis; Lars G Engstrand; Jeffrey I Gordon Journal: Curr Opin Microbiol Date: 2006-01-06 Impact factor: 7.934
Authors: Bhaumik B Patel; Yingjie Yu; Jianhua Du; Edi Levi; Phillip A Phillip; Adhip P N Majumdar Journal: Biochem Biophys Res Commun Date: 2008-11-14 Impact factor: 3.575
Authors: Shigeo Takaishi; Tomoyuki Okumura; Shuiping Tu; Sophie S W Wang; Wataru Shibata; Ramanathan Vigneshwaran; Shanisha A K Gordon; Yutaka Shimada; Timothy C Wang Journal: Stem Cells Date: 2009-05 Impact factor: 6.277
Authors: Edi Levi; Sandhya Misra; Jianhua Du; Bhaumik B Patel; Adhip P N Majumdar Journal: Biochem Biophys Res Commun Date: 2009-05-22 Impact factor: 3.575
Authors: Yoon Jin Choi; Nayoung Kim; Hye Seung Lee; Seon Mee Park; Ji Hyun Park; Hyuk Yoon; Cheol Min Shin; Young Soo Park; Jin-Wook Kim; Dong Ho Lee Journal: J Cancer Prev Date: 2016-12-30
Authors: Lulu Farhana; Fadi Antaki; Mohammad R Anees; Pratima Nangia-Makker; Stephanie Judd; Timothy Hadden; Edi Levi; Farhan Murshed; Yingjie Yu; Eric Van Buren; Kulsoom Ahmed; Gregory Dyson; Adhip P N Majumdar Journal: Cancer Med Date: 2016-03-14 Impact factor: 4.452