A variety of molecular crosstalks between extracellular matrices and their cell surface receptors in oral carcinomas

口腔癌细胞外基质与其细胞表面受体之间的各种分子串扰

• 批准号: 10470379
• 负责人: SAKU Takashi
• 金额: $ 8.13万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470379/
• 关键词: extracellular matrix; heparan sulfate proteoglycan; fibronectin; integrin; adenoid cystic carcinoma; in-situ hybridization; ACC3; alternative splicing; 腺様歯原性腫瘍; 口腔粘膜; ファイブロクネクチン; 口腔癌; オリゴ糖鎖

We have analyzed biosynthesis of extracellular matrix(ECM)molecules by oral carcinoma cells, such as ACC3 established from a human adenoid cystic carcinoma cells, MK-1 and ZK-1 established from oral squamous cell carcinomas. These carcinoma cells were shown to produce basement membrane-associated molecules, especially basement membrane type heparan sulfate proteoglycan, HSPG/perlecan, and fibronectin, FN.These two ECM molecules were different in molecular weight with cell types. We examined the molecular background for the variations in molecular size among them, by using immunoprecipitation of 35S-methionin labeled cells with several combinations of oligosaccharide lyases. ACC3 cells produced high molecular weight HSPG/FN, which were resulted from larger proteins due to alternative splicing and addition of N-and O-linked oligosaccharide chains, although more investigations are necessary for the alternative splicing mechanism for HSPG core protein.Similarly, integrins, INTs, receptors … More for ECM molecules, expressed by these cells were different in size. This was mainly due to oligosaccharide additions. Thus, there was a variety of structures of ECM molecules and their receptors among oral carcinoma cells. Since the molecular sizes were parallel with the attachment ability of the cells, it is suggested that the ECM molecular size, which is varied with carcinoma cell types, regulate the biological nature of them.Such a variety of molecular crosstalks between ECM molecules and their receptors should be also reflected to the tissue architecture of oral carcinomas as well as tissue remodeling processes of granulation tissues. We also immunolocalized these molecules in oral neoplastic and inflammatory lesions. In relation to these immunohistochemical experiments, we proposed a guideline for enzymatic pretreatments for ECM molecules in various tissue types.These results clearly indicate that the molecular structures of ECM molecules and their receptors vary with cell types and that the molecular variety should be reflected in their clinical courses. However, it is unknown from the present study what regulates such molecular variety and if these varieties are actually functions in human carcinoma tissues in vitro. Less

我们分析了口腔癌细胞，如从人腺样囊性癌细胞中建立的ACC 3，从口腔鳞状细胞癌中建立的MK-1和ZK-1细胞的细胞外基质（ECM）分子的生物合成。结果表明，这些癌细胞产生基底膜相关分子，尤其是基底膜型硫酸乙酰肝素蛋白多糖（HSPG/perlecan）和纤维连接蛋白（FN），这两种ECM分子的分子量因细胞类型而异。我们研究了它们之间的分子大小的变化的分子背景，通过使用免疫沉淀的35 S-甲硫氨酸标记的细胞与几种组合的寡糖裂解酶。ACC 3细胞产生高分子量的HSPG/FN，这是由于选择性剪接和添加N-和O-连接的寡糖链而导致的较大的蛋白质，尽管对于HSPG核心蛋白的选择性剪接机制需要更多的研究。 ...更多信息 对于ECM分子，由这些细胞表达的大小不同。这主要是由于低聚糖的添加。因此，口腔癌细胞间存在多种ECM分子及其受体的结构。由于ECM分子的大小与细胞的粘附能力是平行的，因此，ECM分子的大小因癌细胞类型的不同而不同，这表明ECM分子与其受体之间的分子交联在口腔癌的组织结构和肉芽组织的组织重建过程中也有反映。我们还免疫定位这些分子在口腔肿瘤和炎症病变。在这些免疫组化实验中，我们提出了一个指导原则，酶预处理ECM分子在各种组织types.These结果清楚地表明，ECM分子及其受体的分子结构与细胞类型不同，分子多样性应反映在他们的临床课程。然而，从目前的研究中还不知道是什么调节这种分子多样性，以及这些多样性是否在体外人类癌组织中实际上起作用。少

项目成果

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Yonemochi, H.et al.: "Immunohistochemical localization of extracellular matrix molecules in complex odontoma."Dentistry in Japan. 35. 13-19 (1999)

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Toyoshima, K. et al.: "High-molecular-weight fibronectin synthesized by adenoid cystic carcinoma cells of salivary gland origin"Japanese Journal of Cancer Research. 90(3). 308-319 (1999)

Toyoshima，K.等人：“由唾液腺起源的腺样囊性癌细胞合成的高分子量纤连蛋白”日本癌症研究杂志。

Murata, M.: "Enamel protein S and extracellular matrix molecules are co-localized in the pseudocystic stroma space of adenomatoid odontogenic tumor."Journal of Oral Pathology & Medicine. 29(10). 483-490 (2000)

Murata, M.：“牙釉质蛋白 S 和细胞外基质分子共定位于腺瘤样牙源性肿瘤的假囊性基质空间。”口腔病理学杂志

Abe, M.et al.: "The availability and application of enzymatic pretreatments in immunohistochemical study for basement membrane related extracellular matrix molecules."Pathology and Clinical Medicine. 17(5). 515-520 (1999)

Abe, M.等人：“酶预处理在基底膜相关细胞外基质分子免疫组织化学研究中的可用性和应用。”病理学和临床医学。