2007 Fiscal Year Final Research Report Summary
Inhibitory effect of lumican on the growth factor-mediated pancreatic cancer cell growth
| Project/Area Number |
18591526
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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 |
ISHIWATA Toshiyuki Nippon Medical School, Faculty of Medicine, Associate Professor (90203041)
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| Co-Investigator(Kenkyū-buntansha) |
NAITO Zenya Nippon Medical School, Graduate School of Medicine, Professor (20237184)
KUDO Mitsuhiro Nippon Medical School, Faculty of Medicine, Senior Assistant Professor (20256978)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Lumican / pancreatic cancer / Growth factor / glycosylation |
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| Research Abstract |
Lumican is a member of a small leucine-rich proteoglycan family and its overexpression has been reported in carcinoid tumor and in breast, colorectal, neuroendocrine cell, uterine cervical and pancreatic cancers. The expression of lumican in stromal tissues in breast cancer is associated with a high tumor grade, a low estrogen receptor expression level, and young age at on set. Furthermore, lumican expression in the cytoplasm in advanced colorectal cancer is weakly correlated with the spread of lymph node metastasis and depth of tumor invasion, and strongly correlated with a poor prognosis. Reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analyses demonstrated lumican mRNA and protein expression in six pancreatic ductal adenocarcinoma (PDAC) cell lines (ie. PANC-1, MIA PaCa-2, KLM-1, Capan-1, PK-1 and PK-8). Molecular weights of lumican in the cytoplasm of pancreatic cancer cells were 37 to 100kD, but lumican in the culture supernatant of the cells was 60-70kD. In pancreatic cancer tissues, lumican was localized in the cytoplasm of cancer cells in 30 of 53 (56.6%) cancer patients, whereas lumican was detected in stromal tissues in 36 of 53 (67.9%) cancer patients. Lumican expression in the cytoplasm of pancreatic cancer cells did not correlate with clinicopathological factors, whereas lumican expression in stromal tissues correlated with female gender, advanced stage, retroperitoneal and duodenal invasion, and residual tumor. Patients with lumican-positive cancer cells tended to survive longer than those with lumican-negative cancer cells (p=0.286), but patients with lumican-positive stromal tissues showed a shorter survival than those with lumican-negative stromal tissues. These findings suggest that lumican in cancer cells and stromal tissues have different glycosylated patterns and lumican in stromal tissues play important roles in the growth and invasion of pancreatic cancer.
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