| Project/Area Number |
15591449
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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 |
Digestive surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
NAITO Zenya Nippon Medical School, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (20237184)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIWATA Toshiyuki Nippon Medical School, Medicine, Associate Professor, 医学部, 助教授 (90203041)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | lumican / pancreatic cancer / proteoglycan / small-leucine-rich proteoglycan / cell growth / pancreatitis / carcinoid / neuroendocrine cell carcinoma / small-leucine-rich proteoglycan / 細胞増殖 |
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| Research Abstract |
Lumican is a member of small leucine-rich proteoglycan family. We previously reported that lumican was predominantly localized in the area of pathological fibrosis including the thickened intima of human coronary arteries, ischemic and reperfused hearts, and acute pancreatitis and chronic pancreatitis(CP)-like lesions adjacent to pancreatic cancer. In the breast cancer tissues, low expression level of lumican is associated with a rapid cancer progression and poor survival. Experimentally, lumican significantly suppressed subcutanesous tumor formation in syngenic mice, with a concomitant decrease in cyclin D1 expression level, and induced and/or enhanced the apoptosis of these cells. Morpholino antisense oligonucleotide against lumican mRNA strongly inhibited the synthesis of lumican protein in the human embryonic kidney(HEK) 293 cells, and the HEK 293 cell growth rate was higher than those in the control groups. These findings may indicate that lumican protein has an inhibitory effect on HEK 293 cell growth in vitro. The expression of lumican in neuroendocrine(NE) cell tumors including carcinoid tumors and NE carcinoma were examined, and whether the presence of lumican may be associated with the growth of NE tumors were elucidated. Immunohistochemically, the positivity rates of lumican expression in the cytoplasm of the tumor cells were 87.5% in carcinoid tumors and 37.5% in NE carcinomas. Those of lumican expression in stromal adjacent to the tumors were 90.1% in carcinoid tumors and 79.2% in NE carcinomas. Higher expression level of cytoplasmic lumican in carcinoid tumors than in NE carcinomas may play a role in the slow growth of these tumors. Further studies, including administration of recombinant lumican protein to pancreatic cancer cells or experimental cancer animals may be effective to examine the clinical application of lumican to cancer therapy.
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