Identification of a key molecular regulator of liver metastasis in human pancreatic carcinoma using a novel quantitative model of metastasis in NOD/SCID/_<γ_c>^<null> (NOG) mice.
| Project/Area Number |
16590325
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Tokai University |
|---|
Principal Investigator |
NAKAMURA Masato Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (00164335)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Hitoshi Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (20191273)
SUEMIZU Hiroshi Central Institute for Experimental Animals, 研究員 (40332209)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | Pancreatic cancer / Large intestinal cancer / Malignant melanoma / DNA chip analysis / NOG mouse / Distant metastasis / S100A4 / in vivo / 転移 |
|---|
| Research Abstract |
We developed a reliable new model system for assaying liver metastasis using NOD/SCID/_<γ_c>^<null> (NOG) mice. Seven human pancreatic cancer cell lines were examined for their ability to form diverse metastatic foci in the liver of these mice. Capan-2 and PL45 showed no metastasis when seeded at up to 10^5 cells. In contrast, MIA PaCa-2,AsPC-1 and PANC-1 cells metastasized when seeded at 10^2 cells in 71.4% (5/7), 57.1% (4/7) and 37.5% (3/8) of the mice, respectively. Capan-1 and BxPC-3 cells metastasized when seeded at 10^3 cells in 50% (5/10) and with 12.5% (1/8) of the mice, respectively. Using this model system, we established a highly metastatic cell line, liver metastasized-BxPC-3 (LM-BxPC-3), from liver metastatic foci formed by the relatively poorly metastatic parental BxPC-3 cell line. The gene expression profiles of parental and LM-BxPC-3 cells were compared, and we identified forty-five genes that were either up- or down-regulated more than 4-fold in the LM-BxPC-3 cell line. We validated 9 candidate protein-coding sequences, and examined the correlation between their expression pattern and the in vivo liver metastatic potential of all 7 pancreatic cancer cell lines. Only S100A4 expression correlated with the ability to form liver metastases, as evaluated in our quantitative model of metastasis in NOG mice. These results suggested that S100A4 is a key regulator of liver metastasis in pancreatic cancer, and demonstrate the feasibility of using the quantitative metastasis model to search for and develop new anti-cancer-therapies, and novel drugs against this and other key molecules.
|
Report
(3 results)
Research Products
(12 results)
