1989 Fiscal Year Final Research Report Summary
Preliminary study for developing a new approach to treating malignant salivary gland tumors
| Project/Area Number |
63480443
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
外科・放射線系歯学
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| Research Institution | Osaka University |
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Principal Investigator |
SHIRASUNA Kanemitsu Osaka University School of Dentistry, The First Department of Oral and Maxillofacial Surgery, Associate Professor, 歯学部, 助教授 (30093420)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Salivary gland / Salivary neoplasms / Cytodifferentiation / Cell growth / Growth factors / Induction of differentiation / Cancer therapy |
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| Research Abstract |
Since malignant salivary gland tumors are resistance to radiotherapy and/or chemotherapy, the development of new effective treatment is required. HSG cell line of human salivary gland origin may serve as useful tool for studying the biology of the salivary neoplasms and developing a new therapy. The HSG cells have a fine structure similar to intercalated duct cells and the inoculation of the cells into athymic mice results in production of adenocarcinoma. Cells with various phenotypes including myoepithelial-like cells could be isolated from HSG by repeated single cell cloning, changes of cultured conditions or treatment with certain differentiation inducers, such as dibutyryl cyclic AMP and glucocorticoid, suggesting that HSG is pluripotential in differentiation. Induction of more differentiated stages in HSG resulted in slowing of the growth. Inhibition of tumor growth associated with cytodifferentiation is also found in vivo.
Investigation of HSG in serum free medium suggested that this cell line produce EGF and beta-TGF which are probably involved in growth mechanism as regulator. Moreover, it was found that normal human fibroblasts exert a profound influence on the growth and differentiation of HSG, by an indirect effect involving diffusible factor(s). Partial purification and characterization of the factor(s) produced by the fibroblasts suggests that it may be a novel protein carrying both tumor inhibiting and differentiation inducing activities. These results indicate that induction of cytodifferentiation in HSG is possible, suggesting a therapeutic implication for salivary gland tumors. In order to establish cancer therapy, however, further investigation of molecular mechanism on growth and differentiation regulation of HSG as well as other cell lines of salivary gland tumors is required. Such studies are presently in progress using HSG and new cell lines recently established from adenoid cystic carcinoma.
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