2013 Fiscal Year Final Research Report
Identification of human colorectal cancer stem cells.
| Project/Area Number |
24689036
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
SATO Toshiro 慶應義塾大学, 医学部, 特任准教授 (70365245)
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| Research Collaborator |
MATANO Mami 慶應義塾大学, 医学部, 研究員 (20439889)
TAKANO Ai 慶應義塾大学, 医学部, 研究員 (50647584)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 大腸がん / 幹細胞 |
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| Research Abstract |
We have established intestinal organoids from human intestinal epithelium and applied genome engineering system to organoids. With this approach, we introduced multiple driver mutations into human intestinal organoids to elucidate the mechanism of colorectal carcinogenesis. Furthermore, we knocked-in reporter to LGR5 locus of intestinal organoids using genome editing. Owing to the genetic silencing of Lgr5 promoter, we are attempting to employ other stem cell genetic markers. We also established xenotransplantation system with engineered organoids or colorectal cancer organoids. The organoids were readily engrafted and form tumor recapitulating clinical colorectal cancer. Our results suggest that engineered organoid system provide new insights into the understanding of human colorectal cancer. The platform will be useful not only to elucidate cell biological mechanism of colorectal cancer stem cells but also to apply genetic mutation based drug discovery and personalized medicine.
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Research Products
(29 results)
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[Journal Article] KLF5 regulates the integrity and oncogenicity of intestinal stem cells2014
Author(s)
Nakaya T, Ogawa S, Manabe I, Tanaka M, Sanada M, Sato T, Taketo MM, Nakao K, Clevers H, Fukayama M, Kuroda M, Nagai R
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Journal Title
Cancer Res
Volume: (in press)PMID
Pages: 24626089
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[Journal Article] Macrophages and Dendritic Cells Emerge in the Liver during Intestinal Inflammation and Predispose the Liver to Inflammation2014
Author(s)
Mikami Y, Mizuno S, Nakamoto N, Hayashi A, Sujino T, Sato T, Kamada N, Matsuoka K, Hisamatsu T, Ebinuma H, Hibi T, Yoshimura A, Kanai T
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Journal Title
PLoS One
Volume: 9
Pages: e84619
DOI
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[Journal Article] Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis2013
Author(s)
Huch M, Bonfanti P, Boj SF, Sato T, Loomans CJ, van de Wetering M, Sojoodi M, Li VS, Schuijers J, Gracanin A, Ringnalda F, Begthel H, Hamer K, Mulder J, van Es JH, de Koning E, Vries RG, Heimberg H, Clevers H
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Journal Title
EMBO J
Volume: 32(20)
Pages: 2708-21
DOI
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[Journal Article] Continuous low-dose irradiation by I-125 seeds induces apoptosis of gastric cancer cells regardless of histological origin2013
Author(s)
Takabayashi K, Kashiwagi K, Kawata T, Sato T, Matsuoka K, Hisamatsu T, Takaishi H, Hibi T, Ogata H, Yahagi N, Kitagawa Y, Shigematsu N, Kanai T
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Journal Title
Cancer Biol Ther
Volume: 15
DOI
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[Journal Article] A single strain of Clostridium butyricum induces intestinal IL-10-producing macrophages to suppress acute experimental colitis in mice2013
Author(s)
Hayashi A, Sato T, Kamada N, Mikami Y, Matsuoka K, Hisamatsu T, Hibi T, Roers A, Yagita H, Ohteki T, Yoshimura A, Kanai T
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Journal Title
Cell Host Microbe
Volume: 12;13
Pages: 711-22
DOI
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[Journal Article] Mucosal healing with oral tacrolimus is associated with favorable medium- and long-term prognosis in steroid-refractory/dependent ulcerative colitis patients2013
Author(s)
Miyoshi J, Matsuoka K, Inoue N, Hisamatsu T, Ichikawa R, Yajima T, Okamoto S, Naganuma M, Sato T, Kanai T, Ogata H, Iwao Y, Hibi T
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Journal Title
J Crohns Colitis
Volume: 15;7
Pages: e609-14
DOI
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[Journal Article] Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues2013
Author(s)
Miyake M, Toguchi H, Nishibayashi T, Higaki K, Sugita A, Koganei K, Kamada N, Kitazume MT, Hisamatsu T, Sato T, Okamoto S, Kanai T, Hibi T
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Journal Title
J Pharm Sci
Volume: 102
Pages: 2564-71
DOI
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[Journal Article] TGR5 signalling inhibits the production of pro-inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease2013
Author(s)
Yoneno K, Hisamatsu T, Shimamura K, Kamada N, Ichikawa R, Kitazume MT, Mori M, Uo M, Namikawa Y, Matsuoka K, Sato T, Koganei K, Sugita A, Kanai T, Hibi T
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Journal Title
Immunology
Volume: 139
Pages: 19-29
DOI
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