Analysis of Cell Cycle Regulators and Extracellular Matrices Associated with Cell Proliferation in Salivary Gland Tumors

与唾液腺肿瘤细胞增殖相关的细胞周期调节剂和细胞外基质的分析

• 批准号: 10671700
• 负责人: OGAWA Ikuko
• 金额: $ 2.11万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671700/
• 关键词: Salivary gland tumors; Cell proliferation; Cell cycle regulators; p27; Bcl family; Glycosaminoglycans; Proteoglycans; p16; アグリカン; アポトーシス; bcl-2; bax

1. In ACCs, among various cell cycle regulators, the reduced expression of p27 was most closely related with development and progression and it can be a good indicator for predicting metastasis and poor survival. It was indicated that increased proteasome-mediated degradation after translation may play an important role in the reduction of p27 expression on the basis of the examination using ACC cell lines in vitro. Inhibition of proteasome-mediated degradation of p27 protein may be used as a possible target of a novel therapy for ACC patients.2. Bcl-2 and bax were expressed with varying intensity in salivary gland tumors. Bcl-2 was intensely expressed in acinic cell carcinomas with low proliferative activity, suggesting that the inhibition of apoptosis of tumor cells may play an important role in the tumor progression. On the other hand, poorly differentiated mucoepidermoid carcinoma with high proliferative activity expressed bax more intensely than bcl-2. The promotion of apoplosis a … More nd proliferation may simultaneously occur in such highly proliferative tumors.3.1) Various glycosaminoglycans (GAGs) were present at the small intercellular spaces in epithelial areas as well as in myxoid or chondroid areas in PAs, suggesting their production and secretion by the parenchymal cells. Heparan sulfate(HS) was intensely revealed in the nuclei in the chondroid and some epithelial cells and absent from tumor matrices, but other GAGs were only present in the extracellular matrices(ECM). These findings suggest that HS may be mainly related to modulating cell growth and differentiation rather than contributing to ECM constitution.2) Biglycan and aggrecan were contained in myxoid or chondroid matrices, although decorin and PG-M/versican were present in the true mesenchymal stroma. Aggrecan is a major proteoglycan and may be produced mainly by neoplastic myoepithelial cells.3) It was revealed by immuno-electromicroscopic observations that GAGs and aggrecan are produced by the neoplastic myoepithelial cells. Less

1.在ACC中，在多种细胞周期调节因子中，p27表达减少与发育和进展关系最密切，可以作为预测转移和生存不良的良好指标。有人指出，增加翻译后的蛋白酶体介导的降解可能发挥重要作用，在减少p27表达的基础上，检查使用ACC细胞系在体外。抑制蛋白酶体介导的p27蛋白降解可能成为ACC治疗的新靶点. Bcl-2和Bax在涎腺肿瘤中均有不同程度的表达。Bcl-2在增殖活性低下的腺泡细胞癌中呈强表达，提示抑制肿瘤细胞凋亡可能在肿瘤进展中起重要作用。另一方面，低分化粘液表皮样癌与高增殖活性表达bax比bcl-2更强烈。促进细胞凋亡a ...更多信息 3.1）在PA的上皮区、粘液样区和软骨样区的细胞间隙中存在多种糖胺聚糖（glycosaminoglycans，GAG），表明GAG由实质细胞产生和分泌。硫酸乙酰肝素（HS）在软骨样细胞和一些上皮细胞的细胞核中强烈显示，而在肿瘤基质中不存在，但其他GAG仅存在于细胞外基质（ECM）中。这些结果表明，HS可能主要与调节细胞的生长和分化，而不是ECM的组成。2）双糖蛋白聚糖和聚集蛋白聚糖包含在粘液或软骨样基质，虽然核心蛋白聚糖和PG-M/多功能蛋白聚糖存在于真正的间充质基质。聚集蛋白聚糖是一种主要的蛋白多糖，可能主要由肿瘤性肌上皮细胞产生。3）免疫电镜观察显示，肿瘤性肌上皮细胞产生GAG和聚集蛋白聚糖。少

项目成果

Zhao,M.: "Localization of glycosaminoglycans(GAGS)in pleomorphio adenoma(PA)of・・・"J.Oral Pathol, & Med.. 27. 272-277 (1998)

赵，M.：“糖胺聚糖 (GAGS) 在...的多形性腺瘤 (PA) 中的定位”J. Oral Pathol, & Med.. 27. 272-277 (1998)

Takata,T.: "Reduced expression of p27^<Kip1> in relation to salivary adenoid cystic・・・"Cancer. 86. 928-935 (1999)

Takata, T.：“与唾液腺样囊性病变有关的 p27^<Kip1> 表达减少......”癌症。 86. 928-935 (1999)