|Budget Amount *help
¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1993 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1992 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1991 : ¥600,000 (Direct Cost : ¥600,000)
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).