title: In vivo imaging of Lgr5-positive cell populations using confocal laser endomicroscopy during early colon tumorigenesis.
abstract: OBJECTIVE
  A diagnostic molecular marker for pre-neoplastic lesions, particularly before polyposis, is still lacking. Lgr5 has been broadly accepted as a marker for intestinal cancer stem cells. The aim of this study was to investigate the monitoring of Lgr5( + ) cells as a useful tool for the early diagnosis of premalignant lesions before polyp formation.
  
  
  METHODS
  In vivo molecular imaging was performed to examine colon tumorigenesis in Lgr5-EGFP mice treated with azoxymethane and dextran sodium sulfate. eGFP( +) Lgr5( +) regions in the descending colon were longitudinally monitored using side-view confocal endomicroscopy. Based on the eGFP signal intensity on the luminal surface, polyps were classified into two groups - Lgr5-high and Lgr5-low. White light colonoscopy was used to monitor polyp formation.
  
  
  RESULTS
  Approximately 75 % of the polyps originated from foci containing Lgr5-eGFP( +) cells, whereas 25 % of the polyps emerged from Lgr5( -) foci. Among eGFP( +) foci, Lgr5-high foci grew faster than Lgr5-low foci.
  
  
  CONCLUSIONS
  Polyps developed at Lgr5( +) regions. Luminal Lgr5 expression was correlated with the growth rate of early-stage adenomas. Lgr5 is a promising molecular marker for the early diagnosis of colon tumors.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Biomedical Engineering R&D Center, Asan Institute for Life Sciences, Asan Medical Center and University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jun Ki
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Myunghwan
authors.initials: M
authors.lastname: Choi
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Yi Rang
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Yun
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis; D002471:Cell Transformation, Neoplastic; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D003110:Colonic Neoplasms; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D003952:Diagnostic Imaging / Q000379:methods*; D042241:Early Diagnosis; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods*; D009374:Neoplasms, Experimental; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled