1996 Fiscal Year Final Research Report Summary
Interaction if Cell Adhesion Molecules and Tumor Cells on the Production of Matrix Metalloprotease in Gynecological Cancers
| Project/Area Number |
06671662
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
SAITO Toshiaki KYUSHU UNIVERSITY,DEPARTMENT OF GYNECOLOGY AND OBSTETRICS,ASSISTANT PROFESSOR, 医学部, 講師 (80162212)
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| Co-Investigator(Kenkyū-buntansha) |
SHIGEMATU Toshiyuki KYUSHU UNIVERSITY,DEPARTMENT OF GYNECOLOGY AND OBSTETRICS,RESEARCH ASSOCIATE, 医学部, 助手 (30253438)
KOBAYASHI Hiroaki KYUSHU UNIVERSITY,DEPARTMENT OF GYNECOLOGY AND OBSTETRICS,RESEARCH ASSOCIATE, 医学部, 助手 (70260700)
KAKU Tsunehisa KYUSHU UNIVERSITY,DEPARTMENT OF GYNECOLOGY AND OBSTETRICS,RESEARCH ASSOCIATE, 医学部, 助手 (60185717)
KAMURA Toshiharu KYUSHU UNIVERSITY,DEPARTMENT OF GYNECOLOGY AND OBSTETRICS,ASSOCIATE PROFESSOR, 医学部, 助教授 (30152870)
HIRAKAWA Toshio KYUSHU UNIVERSITY,DEPARTMENT OF GYNECOLOGY AND OBSTETRICS,RESEARCH ASSOCIATE, 医学部, 助手 (20218770)
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| Project Period (FY) |
1994 – 1996
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| Keywords | matrix metalloprotease / fibronectin / laminin / invasion / ovarian cancer / uterine cancer / cell adhesion molecules / fibroblast |
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| Research Abstract |
We have investigated the interaction of extracellular integrin ligands and tumor cells on the invasion of gynecological cancer cells.
1.An in vitro invasion assay was used as the model system to study the effect of 3T3 fibroblast conditioned medium (FCM), human uterine fibroblasts conditioned medium (HUFCM), purified human fibronection and laminin on the invasion of cervical carcinoma cells. The 3T3 FCM and HUFCM significantly enhanced the invasion of a cervical carcinoma cell lines, HeLa, SiSo, CAC-1 and TMCC.This enhancement of invasion was inhibited by anti-fibronectin antibody. Purified fibronectin, laminin alone enhanced the invasion in a dose-dependent anner for all cell lines. The pretreatment of cells with cell binding aminossequences, GRGDSP and/or YIGSR blocked the enhancement of cell invasion.
2.Pretreatment of 3T3 fibroblasts and human uterine fibroblasts by TGF-beta ascorbic acid significantly enhanced the invasion of cervical cancer cells. This treatment also enhanced the production of fibronectin by fibroblasts.
3.Usng the zymogram assay, MMP-2 expression of ovarican cancer cells and cervical cancer cells were evaluated. One of the 2 cell lines of ovarian cancer cells and HeLa cells expressed 62kD matrix. metalloproteinase. Both of in vivo cisplatin resistant cell strains aquired the MMP-2 expression. The expression of MMP-2 of HeLa was enhanced by addition of fibronectin in the culture medium.
4.Consequently, gynecolgic cancer cells may induce the enhanced production of fibronectin in surrounding stromal fibroblasts. Cellular fibronectin can induce or enhance the invasion of cancer cells by enhancement of the expression of MMP-2 by tumor cells.
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