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ヒト唾液腺腺癌細胞が産生する骨形成因子と骨誘導に関する研究

人唾液腺癌细胞骨形态发生因子及骨诱导的研究

基本信息

批准号：
03670851
负责人：
HATAKEYAMA Setsuko
金额：
$ 1.34万
依托单位：
Iwate Medical University
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

项目摘要

1. Northern and Western blottings demonstrated that human salivary adenocarcinoma cell's subclone (HSG-S8) expressed bone morphogenetic protein (BMP)-2mRNA, and secreted BMP proteins into the medium in serum free culture. BMP-1, -3, and -4 mRAN were not expressed. Retinoic acid (RA, all-trans, 1 mu M) strongly up-regulated the expression of BMP-2 mRNA by the treatment for 6-48 hrs. The BMP-2 proteins in conditined medium also increased 5-fold by the treatment of 1 mu M RA for 48 hrs. Simultaneously, RA suppressed the growth of HSG-S8 cells through down-regulation of the expression of c-myc. Cells did not show particular morphological features of cellular differentiation by treatment of RA.2. When HSG-S8 cells transplanted into athymic nude mice subcutaneously or intramauscularly, these cells also produced BMP-2 and focally secreted in vivo, which induced heterotopic ossification (s.c.) and cartilage formation (i.m) in the tumos formed by HSG-S8.3. Immunohistochemistry did not show imunoreations of both of anti-BMP-2(from Genetics Institute R230) and -3(from Genetics Institute, SM10) antibodies to celles of the parotid, submandibular, palatal, and labial glands. Only anti-BMP-1 anti-body immunoreacted to degenerated acinar cells of the submandibular gland. In pleomorphic adenoma, the glandular, solid plasmacytoid, and some spindle tumor cells were positive to anti-BMP(s) antibodies. These findings were observed not only in pleomorphic adenoma with cartilage area, but also without cartilage. In cartilage area, some cells were positive to BMP(s). It was suggested that other factors related to the formation of cartilage area in pleomorphic adenoma.

1.北方印迹和Western印迹显示，人涎腺腺癌细胞亚克隆（HSG-S8）表达骨形态发生蛋白（BMP）-2mRNA，并在无血清培养中分泌BMP蛋白。BMP-1、BMP-3和BMP-4 mRNA均不表达。视黄酸（RA，all-trans，1 μ M）处理6-48小时，可显著上调BMP-2 mRNA的表达。经1 μ M RA处理48小时后，条件培养基中BMP-2蛋白表达量增加了5倍。同时，维甲酸通过下调c-myc基因的表达抑制HSG-S8细胞的生长。细胞没有显示出特定的形态特征的细胞分化的处理RA。当将HSG-S8细胞皮下或肌肉内移植到无胸腺裸鼠体内时，这些细胞也产生BMP-2并在体内局灶性分泌，其诱导异位骨化（s.c.）和软骨形成（i.m）。免疫组化未显示抗BMP-2（来自Genetics Institute R230）和抗BMP-3（来自Genetics Institute，SM 10）抗体对腮腺、下颂、腭和唇腺细胞的免疫反应。只有抗BMP-1抗体免疫反应的变性腺泡细胞的下颌下腺。在多形性腺瘤中，腺性、实性浆细胞样和一些梭形肿瘤细胞抗BMP（s）抗体阳性。这些发现不仅见于有软骨区的多形性腺瘤，也见于无软骨区的多形性腺瘤。软骨区部分细胞BMP阳性。提示多形性腺瘤软骨区的形成还与其他因素有关。