1997 Fiscal Year Final Research Report Summary
Identification and Cloning of an inhibitor of Cancer Metastasis and Invasion
| Project/Area Number |
08671882
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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 |
Obstetrics and gynecology
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| Research Institution | Nagoya University |
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Principal Investigator |
KIKKAWA Fumitaka Nagoya Univ.School of Med., Lecturer, 医学部, 講師 (40224985)
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| Co-Investigator(Kenkyū-buntansha) |
NOMURA Seiji Nagoya Univ.School of Med., Research Assistant, 医学部, 助手 (20242860)
OKAMOTO Tomomitsu Nagoya Univ.School of Med., Research Assistant, 医学部, 助手 (70252236)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Ovarian Cancer / Metastasis / Fibronectin / MMP |
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| Research Abstract |
Conditioned media of normal peritoneal, myometrial, and ovarian tissues increased MMP-2 and -9 secretion from ovarian cancer (NOM1) cells in a concentration dependent manner. Especially, MMP-9 was markedly augmented by addition of normal peritoneal tissue conditioned medium. To estimate MMP-9 stimulating factors, conditioned medium of normal peritoneal tissue was fractionated and the influence of each fraction on MMP-9 secretion was examined by zymography. More than 100 kD fraction increased mostly MMP-9 secretion from NOM1 cells. Extracellular matrix, laminine, fibronectin, and type IV collagen, were added to NOM1 cells to identify the more than 100 kD factors. Fibronectin could increase MMP-9 secretion from NOM1 cells in a concentration dependent manner. Furthermore, fibronectin induced secretion of MMP-9 was inhibited by pretreatment with RGD peptides (fibronectin receptor) and antibody against integrin alpha5 receptor. Concentration of fibronectin was 164 ng/ml after 24 hours-culture of normal peritoneal tissue. Since 100 ng/ml fibronectin was enough to stimulate MMP-9 secretion from ovarian cancer cells, fibronectin was suggested to be an important stimulating factor.
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