| Co-Investigator(Kenkyū-buntansha) |
MIYACHI Yoshiki Kyoto Univ., Fac of Medicine, Assist.Professor, 医学部, 講師 (30127146)
TANAKA Toshihiro Kyoto Univ.,Fac. of Medicine,Instructor, 医学部, 助手 (50188314)
FURUKAWA Fukumi Kyoto Univ.,Fac.of Medicine.Assist.Professor, 医学部, 講師 (40156964)
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| Budget Amount *help |
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Research Abstract |
A new subclone, pam-T, was isolated from a parental murine transformed keratinocytes cell line, pam 212. Subcutaneously injected pam-T cells produced squamous cell carcinoma(SCC) in mice with marked peripheral invasiveness to result in the induction of lethal peritonitis in the hosts. *-1-d, *-1 or F-2, were also established from the tumors generated in nude mice skin by the repetitive ultraviolet light irradiations. *-1-d, and *-1 cells induced subcutaneous fibrosarcoma. F-2 injected into the nude mice skin showed rapid formation of a hemorrhagic tumor, whose microscopic examinations revealed that the tumor was composed by a blood-filled cyst. In vitro observations on F-2 cells, including "cobblestone"appearance at confluency, accelerated uptake of fluorescent-labeled acetylated LDL, positive binding of the lectin, GSA-I and rapid tube formation on Martigel, strongly suggested that F-2 was originated from cutaneous vascular endothelial cells. F-2 induced tumor bearing mice were brough
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t to death, mainly by the tumor peripheral invasiveness with resultant heavy bleeding. With those novel cell lines, in vivo cutanous tumor models of SCC, fibrosarcoma and angiosarcoma were successfully established. With these models, the effects of cytokines on the tumors were examined. Interferon-gamma(IFN-gamma) gene was transferred to pam-T cells and IFN-gamma producing clones were isolated. IFN-gamma producing clones exibited similar in vivo tumorigenesity to control IFN-gamma non producing clone, but the mean survival period of the mice bearing IFN-gamma producing clones was significantly elongated compared with that of control mice. Systemic application of interleukin 2(IL-2) to F-2 bearing mice showed that IL-2 significantly suppressed the tumorigenic activity of F-2 cells and elongated the mean survival time of the tumor bearing mice. Those findings may suggest that newly established murin tumors in vivo models are very useful for basic as well as clinical investigations on cutaneous tumors. Less
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