1993 Fiscal Year Final Research Report Summary
Differentiation Induction of a Cell Line with a Monoclonal Antibody
| Project/Area Number |
03807040
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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 |
内科学一般
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| Research Institution | Ehime University School of Medicine |
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Principal Investigator |
KOHNO Nobuoki Ehime University school of medicine, Lecturer, 医学部・附属病院, 講師 (80215194)
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| Project Period (FY) |
1991 – 1993
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| Keywords | differentiation / breast cancer / monoclonal antibody / growth inhibition / cell adhesion |
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| Research Abstract |
We studied the differentiation-induction of a breast cancer cell line, YMB-S, from the aspects of growth suppression and acquired cell adhesiveness.
Molecules concerned with the adhesiveness were alpha3, alpha5, alphav and beta1 integrins, and E-cadherin. The expression levels of these adhesion molecules were significantly increased in the cells treated with sodium butyrate (NaB) compared with the non-treated cells. E-cadherin and alpha3beta1 integrin localized in the site of cell-cell adhesion. Other integrins and extracellular matrix such as fibronectin, laminin and collagens existed diffusely on cell surface.
Differentiation inducers such as 5-azacytidine, n-butyric acid and hexamethylene bisacetamide as well as NaB, dimethyl sulfoxide and dimethylformamide induced differentiation of YMB-S cells. Cycloheximide and actinomycin D suppressed partially the differentiation inducing effects of these differentiation inducers, while each of them alone had similar effects on the cells. These observations indicate that YMB-S cells require both syntheses and synthesis inhibition of protein and/or mRNA to differentiate.
It was proven that KL-6 antibody recognizes human MUC-1 mucin (The 3rd IASLC International Workshop on Lung Tumor and Differentiation Antigens. In Zurich. September 9-11,1993). Similar to NaB, KL-6 antibody induced the adhesion of YMB-S cells and inhibited the growth to induce the cells into G0/G1 phase of cell cycle. In vivo effects of KL-6 antibody were tested on the growth of YMB-S cells. Twenty million cells of YMB-S were inoculated subcutaneously into a nude mouse, KL-6 antibody (1 mg) was i.p.injected 14 times in the duration of 7weeks. KL-6 antibody inhibited significantly the growth of the innoculated YMB-S cells compared with a control murine monoclonal antibody (p<0.05, 10mice in each group).
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[Publications] N.Kohno, Y.Awaya, T.Oyama, M.Yamakido, M.Akiyama, Y.Inoue, A,Yokoyama, H.Hamada, S Fujioka, K.Hiwada: "KL-6, a mucin-like glycoprotein, in broncho-alveolar lavage fluid from patients with interstitial lung disease." Am.Rev.Respir.Dis.148. 637-642 (1993)
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