2006 Fiscal Year Final Research Report Summary
Development of new therapy targeting against factors specifically expressed in vessels of cancerous tissues for cancer of digestive system
| Project/Area Number |
17591372
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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 | Chiba University |
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Principal Investigator |
YOSHITOMI Hideyuki Chiba University, Graduate School of Medicine, Assistant, 医学部附属病院, 助手 (60375631)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Masaru Chiba University, Graduate School of Medicine, Professor, 大学院医学研究院, 教授 (70166156)
KIMURA Fumio Chiba University, Graduate School of Medicine, Assistant Professor, 大学院医学研究院, 助教授 (70334208)
KATO Atsushi Chiba University, Graduate School of Medicine, Assistant, 医学部附属病院, 助手 (70344984)
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| Project Period (FY) |
2005 – 2006
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| Keywords | pancreatic cancer / vascular endothelial cells / angiogenesis / lymphangiogenesis / molecular target therapy |
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| Research Abstract |
Pancreas cancer is one of common deaths from cancer, especially in digestive disease. Despite the recent advances of treatments, the prognosis remains poor with 5-yesr survival rate of less than 5%. It is urgently needed for developing new therapy for this disease. It is known that angiogenesis plays important roles in cancer development It is well characterized that the angiogenesis also involves in the growth and metastasis of pancreatic cancer. In this study, we focused on understanding the mechanism of angiogenesis of pancreatic cancer and search the possibility for developing new antiangiogenetic therapy
To examine the angiogenetic mechanism, we focused on the expression of endoglin. Endoglin is known to be a part of TGF-I3 receptor and involves in vascular development Recently, it is shown that tumor, but not normal tissue, vascular endothelial cells expresses endoglin in breast, colon and brain tumors. We examined whether endoglin expression is restricted in tumor vessels. We use
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d surgically resected pancreatic cancer tissues from 36 patients who had pancreatectomy in Department of general surgery, Chiba University Hospital, Japan between 2001and 2004. First, we did immunostaing using anti-endoglin, anti-Platelet Endothelia Cell Adhesion Molecule (PECAM) antibody on sequential sections. PECAM is known as a vascular endothelial cell marker. In normal pancreatic tissues, adjacent to cancer, PECAM positive vascular endothelial cells could not be stained with anti-endoglin antibody. In contrast, all 36 samples showed that there were endoglin and PECAM double positive cells in cancer tissues. Especially vessels with thin wall and small diameter showed strong endoglin expression. Contrary to this, endothelial cells of arteries with thick wall consistent of tunica media expressed PECAM but not endoglin, even in tumor tissues. These observations suggested that endoglin is expressed in vessels newly formed by tumor angiogenesis but not in mature vessels. Precise observation of these immunostaining showed that there were several endothelial cells which expressed endoglin but not PECAM. Because of this fact, we examined whether lymphatic vessels expressed endoglin. For this purpose, we performed immunostaining using D2-40 antibody, which is specific marker of lymphatic endothelial cells. Interestingly, in tumor tissues, there were endothelial cells stained with both D2-40 and anti-endoglin antibodies. In contrast, D2-40 positive endothelial cells in adjacent normal pancreatic tissue did not express endoglin. These facts suggest that endoglin is expressed in endothelial cells of lymphatic vessels newly formed by tumor lymphangiogenesis.
We next examined that the number of endoglin positive vessels in tumor was correlated with patients' prognosis. Under the same condition with magnification, we measured micro vessel density (MVD) in pancreatic cancer tissues. We counted MVD assessed by endoglin staining (endoglin-MVD) and by PECAM staining (PECAM-MVD). As expected, endoglin-MVD and PECAM-MVD showed strong correlation. PECAM-MVD did not showed correlation with both disease free survival time and overall survival time. In contrast, patients with lower endoglin-MVD in cancer tissues experienced longer disease free survival and overall survival time than higher endoglin-MVD patients. This fact indicate that angiogenesis and lymphangiogenesis play important roles in cancer growth and metastasis.
Our data strongly indicate that endoglin has a strong potential as a new target of anti-angiogenic and lymphangiogenic therapy against pancreatic cancer. Less
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Research Products
(4 results)
