Differentiation Induction of a Cell Line with a Monoclonal Antibody

用单克隆抗体诱导细胞系的分化

• 批准号: 03807040
• 负责人: KOHNO Nobuoki
• 金额: $ 1.15万
• 依托单位: Ehime University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03807040/
• 关键词: differentiation; breast cancer; monoclonal antibody; growth inhibition; cell adhesion; 分化; インテグリン; エストロ-ゲン・リセプタ-; モノクロ-ナル抗体

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).

我们从细胞生长抑制和获得细胞黏附的角度研究了乳腺癌细胞株YMB-S的分化诱导作用，与黏附有关的分子有α3、α5、αv和β1整合素以及E-钙粘附素。与未处理的细胞相比，经丁酸钠(NAB)处理的细胞中这些黏附分子的表达水平显著增加。E-钙粘附素和α-3beta1整合素定位于细胞-细胞黏附部位。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、二甲基亚砜、二甲基甲酰胺等分化诱导剂对YMB-S细胞具有诱导分化作用。放线菌素D和放线菌素D可部分抑制这两种分化诱导剂的诱导分化作用，但单独使用时对细胞的诱导分化作用相似。这些观察结果表明，YMB-S细胞需要蛋白质和/或基因的合成和合成抑制才能分化。KL-6抗体被证明识别人MUC-1粘蛋白(第三届国际肺肿瘤与分化抗原国际研讨会)。在苏黎世。1993年9月9日至11日)。KL-6抗体能诱导YMB-S细胞黏附，抑制细胞生长，诱导细胞进入G0/G1期。体内实验检测KL-6抗体对YMB-S细胞生长的影响。将YMB-S细胞接种于裸鼠皮下，连续注射KL-6抗体(1 Mg)14次，共7周。KL-6抗体显著抑制未接种的YMB-S细胞的生长，与对照组(P&lt；0.05，每组10只小鼠)相比，KL-6抗体显著抑制细胞的生长。

项目成果

H.Hamada, N.Kohno, K.Hiwada: "A new serum tumor marker, CAM 123-6, highly specific to pulmonary adenocarcinoma." Jpn.J.Cancer Res.85. 211-219 (1994)

H.Hamada、N.Kohno、K.Hiwada：“一种新的血清肿瘤标志物 CAM 123-6，对肺腺癌具有高度特异性。”

N.Kohno, Y.Inoue, H.Hamada, S.Fujioka, S.Fujino, A.Yokoyama, K.Hiwada, N.Ueda, M.Akiyama.: "Difference in sero-diagnostic values among KL-6-associated mucins classified as cluster 9." Int.J.Cancer. Supplement, (in press). (1994)

N.Kohno、Y.Inoue、H.Hamada、S.Fujioka、S.Fujino、A.Yokoyama、K.Hiwada、N.Ueda、M.Akiyama.：“KL-6 相关血清诊断值的差异

N.Kohno et al.: "Difference in sero-diagnostic values among KL-6-associated mucins classified as cluster 9" International Journal of Cancer. (1994)

N.Kohno 等人：“分类为第 9 簇的 KL-6 相关粘蛋白之间血清诊断值的差异”国际癌症杂志。

H.Hamada et al.: "A new serum tumor marker,CAM 123-6,highly specific to pulmonary adenocarcinoma." Japanese Journal of Cancer Research. 85. 211-219 (1994)

H.Hamada 等人：“一种新的血清肿瘤标志物 CAM 123-6，对肺腺癌具有高度特异性。”

NOBUOKI KOHNO: "A Circulating heat-nesstant mucin-like antizen in patients with lung ccuncer detected by a new murine monoclonil artibody" International Journal of Onolugy. 1. 649-655 (1992)

NOBUOKI KOHNO：“通过一种新的鼠单克隆抗体检测到肺癌患者的循环耐热粘蛋白样抗原”国际 Onolugy 杂志。