Characterization of LGR5 stem cells in colorectal adenomas and carcinomas.
LGR5 is known to be a stem cell marker in the murine small intestine and colon, however the localization of LGR5 in human adenoma samples has not been examined in detail, and previous studies have been limited by the lack of specific antibodies. Here we used in situ hybridization to specifically examine LGR5 mRNA expression in a panel of human adenoma and carcinoma samples (n = 66). We found that a small number of cells express LGR5 at the base of normal colonic crypts. We then showed that conventional adenomas widely express high levels of LGR5, and there is no evidence of stereotypic cellular hierarchy. In contrast, serrated lesions display basal localization of LGR5, and the cellular hierarchy resembles that of a normal crypt. Moreover, ectopic crypts found in traditional serrated adenomas show basal LGR5 mRNA, indicating that they replicate the stem cell organization of normal crypts with the development of a cellular hierarchy. These data imply differences in the stem cell dynamics between the serrated and conventional pathways of colorectal carcinogenesis. Furthermore we noted high LGR5 expression in invading cells, with later development of a stem cell niche in adenocarcinomas of all stages.
Centre for Tumor Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK, EC1M 6BQ.
Ann-Marie
AM
Baker
Centre for Tumor Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK, EC1M 6BQ.
Trevor A
TA
Graham
Centre for Tumor Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK, EC1M 6BQ.
George
G
Elia
Centre for Tumor Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK, EC1M 6BQ.
Nicholas A
NA
Wright
Department of Histopathology, University College London, London, UK, WC1E 6BT.
Manuel
M
Rodriguez-Justo
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology*; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D011127:Polyps / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D055153:Stem Cell Niche
C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled