| Project/Area Number |
08457442
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Tottori University (School of Medicine) |
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Principal Investigator |
TERAKAWA Naoki Tottori Univ.Dept.Obstet.Gynecol., Professor, 医学部, 教授 (90163906)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Tasuku Tottori Univ.Dept.Obstet.Gynecol., Assistant Professor, 医学部・附属病院, 講師 (40218649)
MINAGAWA Yukihisa Tottori Univ.Dept.Obstet.Gynecol., Assistant Professor, 医学部・附属病院, 講師 (70190692)
KIGAWA Junzo Tottori Univ.Dept.Obstet.Gynecol., Assistant Professor, 医学部, 講師 (00177784)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | Endometrial cancer / Angiogenic factor / Tumor necrosis factor a / Interleukin-8 / Stromal cells / Microvessel density / Cancer growth / Paracrine effect / 子宮内膜 / 子宮内膜症 / 細胞増殖 / IL-8 / TNFα |
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| Research Abstract |
This study was undertaken to find out the candidate of an angiogenic factor (s) in endometrial carcinoma. In recent clinical studies, we have found that the concentration of tumor necrosis factor a (TNF a) in peritoneal fluid of patients with endometriosis was increased and there was a significant correlation between the peritoneal fluid levels of TNF a and interleukin-8 (IL-8). We, therefore, examined the effects of angiogenic factors, TNF a and IL-8, on stromal cells collected from normal endometrium, endometriosis and endometrial carcinoma tissues. Addition of TNF a (0-100pg/ml) to the culture medium increased the production of IL-8 in both endometrial and endometriotic stromal cells, in a dose-dependent manner. The MTT assay showed that the number of endometriotic stromal cells increased in the presence of TNF a, but addition of anti-IL-8-antibody abolished the stimulating effect of TNF a on cell proliferation. IL-8 (200pg/ml) showed a growth-promoting effect on stromal cells of en
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dometrial carcinoma, which was 130% of control values. The expression of transcripts of TNF a receptor II and IL-8 receptor typeA were observed in each stromal cells by RT-PCR and Southern blot analysis.
Hysterectomy specimens of endometrial cancer were stained immunohistochemically for factor VIII-related antigen and anti-IL-8-antibody, and the numbers of the factor VIII-related antigen microvessels and the IL-8-stained vessels per area were counted by light microscopy. The numbers of microvessels in moderately-and poorly differentiated and those of IL-8 stained vessels in poorly differentiated carcinoma were significantly increased, suggesting that microvessel and IL-8-positive vessel densities are correlated with tumor grade. In summary, these results suggest that TNF a exerts paracrine effects on both the stromal and endothelial cells of endometrial carcinoma and stimulates the production of IL-8. The present study also raise the possibility that IL-8 may act as an angiogenic factor in endometrial cancer and promote the cancer growth. Less
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