2010 Fiscal Year Final Research Report
Novel mechanism for the angiogenesis in hepatocellular carcinoma
| Project/Area Number |
20590780
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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 |
Gastroenterology
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| Research Institution | Okayama University |
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Principal Investigator |
SHIRAHA Hidenori Okayama University, 病院, 助教 (40379748)
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| Co-Investigator(Kenkyū-buntansha) |
KOBASHI Haruhiko 岡山大学, 病院, 講師 (00403486)
ONISHI Hideki 岡山大学, 大学院・医歯薬学総合研究科, 助教 (30595468)
NAKAMURA Shinichiro 岡山大学, 病院, 助教 (70514230)
YAMAMOTO Kazuhide 岡山大学, 大学院・医歯薬学総合研究科, 教授 (90140491)
KOBAYASHI Yoshiyuki 岡山大学, 病院, 助教 (20379746)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 細胞増殖 / 肝細胞癌 / 血管新生 |
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| Research Abstract |
Des-gamma carboxy prothrombin (DCP) stimulated KDR in human umbilical vein epithelial cell ; enhanced cell migration by 2.2-fold and enhanced cell proliferation by 1.5-fold. KDR inhibitor abrogated these effects. Sequence analysis revealed that exon 2 skipping splice variant gamma-glutamyl carboxylase (Δ2-GGCX) was expressed in DCP-positive hepatocellular carcinoma (HCC) cells. DCP-positive HCC cells expressed 69% of Δ2-GGCX, while DCP-negative HCC cells expressed 8% of Δ2-GGCX. The introduction of Δ2-GGCX converted DCP-negative HCC cells into DCP-positive HCC cells. On the other hand, the introduction of wild type (WT)-GGCX converted DCP-positive HCC cells into DCP-negative HCC cells. WT-GGCX and Δ2-GGCX expressing Hep3B cells were injected subcutaneously into nude mice. Δ2-GGCX-Hep3B formed more angiogenic tumors and 4.2-fold larger tumors than WT-GGCX-Hep3B. HCC tissue samples demonstrated a positive correlation between DCP production and angiogenesis determined by CD31 index. The serum DCP level of hypervascular HCC was significantly higher than that of hypovascular HCC. In toto, DCP expression is associated with tumor angiogenesis in HCC.
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