2007 Fiscal Year Final Research Report Summary
Role of colonic stem cell crypt fission and carcinogenesis
| Project/Area Number |
18590395
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
TSUKAMOTO Tetsuya Aichi Cancer Center Research Institute, Division of Oncological Pathology, Section Head (00236861)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Min mouse / Chimera mouse / colon crypt / fission / dextran sulfate sodium / cyclooxygenase-2 / stem cell |
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| Research Abstract |
1. Intestinal tumorigenesis in Min mice is enhanced by X-irradiastion in an age-dependent manner with a peak of 2.7-fold increase at 10-12 days of age, whereas exposure at later ages resulted in only a slight increase. To reveal the mechanism of the increased susceptibility, colonic crypts were classified into "Single(S) "and "Bifurcating(B)" types, the former has round bottom and the latter shows division at its bittom. At 12 days old, the radio of B crypts was more than 50% ; at 60 days old only 5%. Nonetheless, bromodeoxyuridine labeling index was the highest in S crypts in 60 days old mice. Thus it was concluded that crypt division was more associated with tumorigenicity than cell proliferation.
2. Patients with ulcerative colitis(UC) are at increased risk of colorectal adenocarcinomas. Dextran sulfate sodium(DSS) has been known to cause severe inflammation in rodents resembling UC and to accelerate colon carcinogenesis. To clarity this mechanism, we have analyzed crypt / cell clonality and proliferation during healing stage of ulcer. Five to six weeks old. C3H<-> Green mouse(C57BL/6J background) chimera mice were given DSS as drinking water for 7 days. The animals were sacrificed at 8, 10, and 14 experimental days one hour after bromodeoxyuridine(BrdU) administration. Colon tissues were routinely processed and analyzed for the expression of C3H specific antigen(CSA), BrdU, and Cox2 as well as histopathological evaluation including the number of crypt fissons. Cox2 was expressed especially in erosive(lacking epithelial) region. Cell production was gradually increased after DSS treatment in crypts neighboring erosion both with cell division and crypt fisson. Erosion was covered with surface epithelial cells provided by the adjacent crypt. Surface epithelial cells coveing erosion began to proliferate in random area in migrating front later in ulcer healing.
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