Differentiation Induction of a Cell Line with a Monoclonal Antibody

我们从生长抑制和获得性细胞粘附性两方面研究了乳腺癌细胞株YMB-S的分化诱导。与粘附性有关的分子有α 3、α 5、α v和β 1整合素以及e -钙粘蛋白。与未处理的细胞相比，经丁酸钠（NaB）处理的细胞中这些粘附分子的表达水平显著增加。E-cadherin和alpha3beta1整合素定位于细胞-细胞粘附部位。其他整合素和细胞外基质如纤维连接蛋白、层粘连蛋白和胶原弥散存在于细胞表面。5-氮杂胞苷、正丁酸、六亚甲基双乙酰胺等分化诱导剂以及NaB、二甲亚砜、二甲甲酰胺等诱导细胞分化。环己亚胺和放线菌素D部分抑制了这些分化诱导剂的诱导分化作用，但单独使用它们对细胞的诱导作用相似。这些观察结果表明，YMB-S细胞需要蛋白质和/或mRNA的合成和合成抑制才能分化。经证实，KL-6抗体可识别人MUC-1粘蛋白（第三届IASLC肺肿瘤与分化抗原国际研讨会）。在苏黎世。1993年9月9 - 11日)。与NaB类似，KL-6抗体诱导YMB-S细胞粘附，抑制细胞生长，诱导细胞进入细胞周期的G0/G1期。在体内检测KL-6抗体对YMB-S细胞生长的影响。裸鼠皮下接种2000万个YMB-S细胞，KL-6抗体（1 mg）灌胃14次，持续7周。与对照组单克隆抗体相比，KL-6抗体显著抑制了接种后小鼠YMB-S细胞的生长（p<0.05，每组10只）。

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).