1997 Fiscal Year Final Research Report Summary
The expression of macrophage colony-stimulating factor and c-fms in the human endometrial and ovarian cancer and its metastatic potential
| Project/Area Number |
07671819
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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 | Saitama Medical School |
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Principal Investigator |
TAKEDA Satoru Saitama Medical School, Associate Professor, 医学部, 助教授 (20143456)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAGI Akiyoshi Saitama Medical School, 医学部, 助手 (80226745)
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| Project Period (FY) |
1995 – 1997
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| Keywords | endometrial cancer / ovarian cancer / M-CSF / c-fms / apoptosis / TNF-alpha / c-AMP |
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| Research Abstract |
Previously we found that the Ishikawa endometrial cancer cell line expresses macrophage colony-stimulating factor (M-CSF) and c-fms transcripts and that its proliferation is enhanced by the addition of recombinant M-CSF.Using retroviral infections to introduce and express exogenous c-fms genes in Ishikawa cells we also demonstrate proliferation to be partially inhibited by a dominant negative, mutant c-fms gene, yet enhanced approximately 3-fold by a normal c-fms gene, under conditions in which the only source of M-CSF was that produced by the cells. The data provide evidence for the existence of an active M-CSF/receptor loop in these endometrial cancer cells and suggests the possibility of such activity in tumors of the endometrium and ovary that aberrantly express M-CSF and c-fms genes.
TNF-alpha, LPS and c-AMP elevating agents such as foskolin, cholera toxin, 8-brom-c-AMP,dibutyryl-c-AMP,and IBMX,inhibited Ishikawa cell growth dosedependently, whereas M-CSF levels in medium were increased by these agents. Phorbol ester, TPA stimulated cell proliferation though protein kinase C pathway. We also demonstrated that TNF-alpha receptor antibody, specifically activating 55kDa TNF-alpha receptor, and TNF-alpha analogue, binding to 55kDa TNF-alpha receptor, induced apoptosis in Ishikawa and ovarian cancer cell lines, using TUNEL method and flow cytomtry.
TNF-alpha, LPS and c-AMP elevating agents inhibited cell proliferation in Ishikawa cells and ovarian cancer cells as well as in macrophage cell lines. It remains to be establishes whether these treatments caused a decrease in the expession of c-fms, and hence diminished sensitivity to M-CSF,despite the fact that the production of M-CSF was stimulated by these agents.
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