1992 Fiscal Year Final Research Report Summary
Fundamental study on the mechanism of invasion and proliferation of uterine cervical cancer cells
| Project/Area Number |
03670801
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Osaka Medical College |
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Principal Investigator |
UEKI Minoru Osaka Medical College Obstet and Gynecol Associate Prof, 医学部, 助教授 (40084892)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Yoshiaki Osaka Medical College Obstet and Gynecol Assistant, 医学部, 助手 (00224080)
UEDA Masatsugu Osaka Medical College Obstet and Gynecol Assistant, 医学部, 助手 (50223467)
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| Project Period (FY) |
1991 – 1992
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| Keywords | uterine cervical carcinoma / proliferation / invasion / extracellular matrix / proteolytic enzymes / growth factors / oncogene / cell culture |
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| Research Abstract |
The mechanism of invasion and proliferation of uterine cervical carcinoma is considered to be closely related to interactions between carcinoma and surrounding stroma. In this study, we investigated how various growth factors act on growth and regulation of extracellular matrix components and their degenerative enzymes in uterine cervical carcinoma cells in vitro. In 1991, we examined the biological role of epidermal growth factor(EGF)(10^<-10>M) and transforming growth factor (TGF)-beta (10^<-11>M) on cell growth and laminin, collagen IV and tissue plasminogen activator(t-PA) production of cultured cervical carcinoma cells(OMC-1 : cervical squamous carcinoma cell line, OMC-4 : cervical adenocarcinoma cell line). OMC-1 cells produced laminin, and OMC-4 cells produced laminin, collagen IV and t-PA in culture media. Laminin and collagen IV were produced by these cells mainly in the logarythmic growth phase. The production of laminin, collagen IV and t-PA by OMC-1 cells was not affected b
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y EGF and TGF-beta, whereas the production of laminin and collagen IV by OMC-4 cells was inhibited by EGF and promoted by TGF-beta, and that of t-PA was significantly promoted by EGF and inhibited by TGF-beta, These results suggested that EGF and TGF-beta might act regulators of extracellular matrix formation and degradation especially in cultured adenocarcinoma cells. In 1992, as a consecutive experiment, we performed above-mentioned procedures, using endometrial adenocarcinoma cell lines(Ishikawa, OMC-2). The growth of both cultured cells were promoted by EGF, and the production of laminin, collagen IV and t-PA by these cells was controlled by EGF and TGF-beta in the same manner as described in OMC-4 cells. These results strongly suggested that these growth factors might be closely associated with the mechanism of construction and destruction of basement membrane components around cervical and endometrial glands in the process of invasion of adenocarcinoma cells. Now we evaluate the invasion ability of carcinoma cells more directly through the mixed culture system of cultured adenocarcinoma cells and normal stromal cells, and moreover investigate the tissue localization of laminin, collagen IV and t-PA in clinical materials of cervical adenocarcinomas immunohistochemically. Less
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