| Project/Area Number |
25460955
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Sapporo Medical University |
|---|
Principal Investigator |
Naishiro Yasuka 札幌医科大学, 医療人育成センター, 講師 (80347161)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
Yoshiaki Arimura 札幌医科大学, 医学部, 講師 (80305218)
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
|---|
| Keywords | 間葉系幹細胞 / 大腸癌細胞 / ニッチ / 骨髄間葉系幹細胞 / MSC依存性腫瘍増殖 / MSCニッチ |
|---|
| Outline of Final Research Achievements |
This study aimed to clarify mechanisms of MSC-dependent tumor progression. Tumor growth progressed in two manners, either independent of or dependent on MSCs. COLO 320 xenograft angiogenesis was CXCL12 dependent but vascular endothelial growth factor (VEGF) less dependent, whereas HT-29 angiogenesis was not CXCL12 but VEGF dependent. MSCs differentiated into pericytes that enhanced angiogenesis as a perivascular niche, which was designated MSC-dependent angiogenesis. CXCL12 was epigenetically inactivated in most colorectal cancer cells except for COLO 320 cells, in which the promoter region was demethylated, but ten eleven translocation 1-3 (TET1-3)/activation-induced cytidine deaminase (AID) did not work as DNA demethylases. Either VEGF overexpression or CXCL12 knockdown was not sufficient for MSC-independent growth. In contrast, the MSC niche conferred an anti-proliferative property to HT-29 cells, through mesenchymal-epithelial transition.
|
