title: Characteristics of carbonic anhydrase 9 expressing cells in human intestinal crypt base.
abstract: Though recent studies have revealed that stem cells of many tissues are harbored in hypoxic microenvironment, little is known about the relationship between hypoxia and intestinal crypt base, where intestinal stem cells are supposed to exist. In this study, we focused on carbonic anhydrase IX (CA9), a hypoxia-inducible membrane-tethered protein, in normal intestinal crypt base, adenoma and early colorectal cancer. Using surgically resected human colorectal cancer specimen, we searched for the expression pattern and functional association of CA9 in human adult normal intestinal epithelia, adenoma and early colorectal cancer by immunofluorescent and immunohistochemical staining, flow cytometry, and quantitative real-time-polymerase chain reaction. We demonstrated that almost all crypt base slender cells in ileum and crypt base cells with eosinophilic structure in their basal cytoplasm in right and left colon were CA9+ with the ratio of 25 to 40%, and that adenoma and T1 colorectal cancer showed broad expression of CA9. Flow cytometrically sorted CA9+ population showed increased mRNA level of a Wnt signaling factor AXIN2. In conclusion, these observations indicate that CA9 expression in normal crypt base cells has association with intestinal epithelial stemness and CA9 may be involved in the carcinogenesis of colorectal cancer.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Haraguchi
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Ohtsuka
authors.affiliation: Department of Surgery, Osaka General Medical Center, Higashi Sumiyoshi-Ku, Osaka 558-0056, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Miyazaki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Uemura
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D060466:Axin Protein / Q000096:biosynthesis* / Q000235:genetics; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: C491761:AXIN2 protein, human; D000951:Antigens, Neoplasm; D060466:Axin Protein; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases