| Co-Investigator(Kenkyū-buntansha) |
NAKAZAWA Tsuneo Sch.of Med., Dept.Yokohama City University Obst.& Gyn., 医学部, 講師 (90254169)
HIRAHARA Fumiki Sch.of Med., Dept.Yokohama City University Obst.& Gyn., 医学部, 教授 (30201734)
宮城 悦子 横浜市立大学, 医学部, 助手 (40275053)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
The histogenesis of carcinosarcoma of the female genital tract is still unknown. Three theories ; a collision tumor, a combination or monophasic tumor including a conversion tumor and a composition tumor, have been postulated, resulting from tissue culture, heterotransplantation, ultrastructural and immunohistochemical studies. A human uterine carcinosarcoma cell line has been established and passed successfully in cell cu1ture for more than 5 years. Seven clones which were obtained by cloning using limiting dilution and/or the collagen substrate-method from EMTOKA cell line were used for further study. The sizes and shapes of the tumor cells from all the EMTOKA clones varied and at least five cell types were distinguished, i.e.columnar, small epithelial, moderately sized or large epithelial-like, malignant tumor giant and spindle-shaped cells, which were all identical to those observed in the EMTOKA cell line from which the clones were isolated. The expression of IFs and other protein
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s in the EMTOKA clones was identical to that in the EMTOKA cell line. It and its seven clones all expressed cytokeratins 8, 17, 18 and 19, vimentin, epithelial membrane antigen, S-100, myoglobin, type II collagen, alpha-smooth muscle actin, placental alkaline phosphatase and epidermal growth factor receptor. The c-erbB-2 and p53 expression levels of all the cell types of the EMTOKA cell line and its clones were the same. Interestingly, an ultrastructural study showed that the EMTOKA cell line and its clones at early and late passages possessed the characteristics of epithelial cell types with neither transitional forms between the epithelial and stromal components nor differentiation into sarcomatous components. Chromosome analysis of the EMTOKA cell line and its clones revealed the modal chromosome number ranged from 61 to 89 and G-banding analysis showed they possessed complex aberrations. The karyotypic abnormalities common to the parental cell line and its clones were : lp^-, 3p^-, 7q^+, 11q^+, +l2p^+ and +l5p^+. PCRamplification of the HUMARA STA of original tumor showed that one of the two alleles was methylated in the lesional tissue whereas both of the alleles were methylated in the normal tissue. The patterns of X-chromosome inactivation were identical in EMTOKA cell line and clones as well as in the original tumor. Heterotransplantation of EMIOKA cells produced the tumors which were interpreted histologically as carcinosarcoma. The results strongly suggest that uterine carcinosarcoma is monoclonal and the cells we established are derived from a common stem cell. Less
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