Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer.
Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a 7-transmembrane receptor reportedly expressed in stem cells of the intestinal crypts and hair follicles of mice. Overexpression of LGR5 is observed in some types of cancer; however, there has been no specific assessment in colorectal tumorigenesis. We performed quantitative RT-PCR for LGR5 expression in 37 representative cancer cell lines, and showed that LGR5 mRNA was frequently overexpressed in colon cancer cell lines. Moreover, LGR5 expression was higher in colon cancer cell lines derived from metastatic tumors compared with those from primary tumors. In clinical specimens, there was significant overexpression of LGR5 in 35 of 50 colorectal cancers (CRCs), and in seven of seven sporadic colonic adenomas, compared with matched normal mucosa. This suggests up-regulation of LGR5 from the early stage of colorectal tumorigenesis. LGR5 expression showed marked variation among CRC cases and correlated significantly with lymphatic invasion, vascular invasion, tumor depth, lymph node metastasis, and tumor stage (IIIC vs. IIIB). In addition to cancer cells, crypt base columnar cells of the small intestine and colon were shown by in situ hybridization to express LGR5. This is the first report suggesting the involvement of LGR5, not only in early events but also in late events in colorectal tumorigenesis.
Uchida
Hiroshi
H
Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
Yamazaki
Ken
K
Fukuma
Mariko
M
Yamada
Taketo
T
Hayashida
Tetsu
T
Hasegawa
Hirotoshi
H
Kitajima
Masaki
M
Kitagawa
Yuko
Y
Sakamoto
Michiie
M
D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
C116884:LGR5 protein, human; C493597:Lgr5 protein, mouse; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D043562:Receptors, G-Protein-Coupled; D007930:Leucine
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