| Project/Area Number |
03670783
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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 University |
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Principal Investigator |
SAWADA Masumi Staff of Department of Obstetrics and Gynecology, Osaka University Medical School, 医学部, 助手 (60226074)
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| Co-Investigator(Kenkyū-buntansha) |
AKEDO Hitoshi Head of Research Institute, The Center for Adult Diseases, Osaka, 所長
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Ovarian cancer / Mesothelial cell / Invasion / Experimental model / In vitro / Azatyrosine / Serum factor |
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| Research Abstract |
To understand the mechanism by which human tumor cell invasion takes place we have tried to establish an experimental model for ovarian tumor cell invasion of mesothelial cell monolayer. Mesothelial cells were isolated from normal rat mesentery. Cultured mesothelial cells (M-cells) grew forming a monolayer like 'pavement stone sheet'. When M-cells grew to a confluent state, tumor cells (1X10^5/dish) were seeded on M-cell monolayer and cultured. Five cell lines derived from human ovarian tumors were tested for their invasive behaviors. Several hours after the tumor cell seeding, the cells adhered to M-cell monolayer and started to penetrate by extending pseudopodia-like cytoplasmic processes through junctional margins of neighboring M-cells, resulting in the formation of penetrated single tumor cells which then proliferate to form colonies. The number of penetrated single tumor cells and colonies/cm^2 increased up to 24 h after the tumor cell seeding and thereafter stayed almost constant. It also increased with the number of tumor cells seeded, when counted at 48 h, therefore was taken to be the invasive ability of tumor cells. The invasive ability of tumor cells varied with the tumor cell lines examined. Tumor cells lost an ability to invade by treatment with azatyrosine. In vitro invasion of mesothelial cell monolayers by ovarian tumor cells occurred in the absence of serum in the assay medium. The serum could be substituted with lysophosphatidic acid (LPA), phospholipase D (PLD). Treatment of tumor cells with cholera toxin abolished the effect of LPA and PLD. These results suggest the participation of a particular signal transduction pathway, PLD-LPA system, in tumor cell invasion. Application of this system appears to provide a rapid determination of the invasive potential of tumor cells and to make it easy to screen substances which modify the invasion of mesothelial cells.
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