The Effects of Alteration of Expression of Cell Adhesion Molecules on Various Morphogenesis amd Biological Behaviors in Salivary Gland Tumors

细胞粘附分子表达的改变对唾液腺肿瘤各种形态发生和生物学行为的影响

• 批准号: 13671905
• 负责人: OGAWA Ikuko
• 金额: $ 0.7万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671905/
• 关键词: Salivary gland tumors; Pleomorphic adenoma; Adenoid cystic carcinoma; Extracellular matrix; Cell adhesion molecules; Matrix metalloproteinase; Cell lines; 基質産生; 基質分解; 予後; in vitro

1. Cell adhesion molecules including E-cadherin,α,β-catenin, CD44v6 and v9 were intensely expressed on cell membranes in normal salivary glands and salivary gland tumors without myoepithelial participation, whereas in pleomorphic adenoma (PA) their expression intensity was reduced even in solid proliferation areas. In Adenoid cystic carcinoma (ACC), E-cadherin and β-catenin were detected on cell membrane, but their distribution exhibited irregularity with tiny spot-like depositions. In a few cases of ACC, β-catenin was present in the nuclei, suggesting that it may play some role in the tumorigenesis of ACC. On the other hand, reduced expression of CD44 variants may be not related to metastatic potential in ACC2. In cases of ACC showing reduced expression of E-cadherin and nuclear expression of β-catenin, overexpression of epidermal growth factor receptor (EGFR) was detected, suggesting that EGF-EGFR pathway may promote various genes through Wint signal transduction3. Extracellular matrices of ACC contained matrix metalloproteinase (MMP) -2 and -9 which may play an important role of destruction of basement membrane, invasion and metastasis of tumor cells4. The immortalized cell lines of PA and acinic cell carcinoma (AC) were obtained by transfection with hTERT gene. The immortalized PA cells were positive for both secretory markers such as lactoferrin and lysozyme and myoepithelial markers such as S-100 protein and calponin. These cells also expressed PLAG1 gene. On the other hand, AC cells expressed only secretory markers. These cell lines may represent a novel in vitro cell model for studies the regulatory mechanism of cellular differentiation and morphogenesis of salivary gland tumors

1.在正常涎腺和无肌上皮参与的涎腺肿瘤中，E-cadherin、α，β-catenin、CD 44 v6和v9等细胞粘附分子在细胞膜上表达较强，而在多形性腺瘤（PA）中，即使在实性增生区，其表达强度也较低。腺样囊性癌（ACC）细胞膜上可见E-cadherin和β-catenin，但分布不规则，呈点状沉积。在少数ACC中，β-catenin表达于细胞核中，提示其可能在ACC的发生发展中起一定作用，而CD 44变异体的表达减少可能与ACC 2的转移潜能无关。在ACC中，E-cadherin表达减少，β-catenin核表达减少，检测到表皮生长因子受体（EGFR）过表达，表明EGF-EGFR途径可能通过Wint信号转导促进各种基因3。ACC细胞外基质中含有基质金属蛋白酶（MMP）-2和-9，可能在基底膜破坏、肿瘤细胞浸润和转移中起重要作用。用hTERT基因转染PA和腺泡细胞癌（AC）细胞，获得永生化细胞株。永生化PA细胞的分泌标志物，如乳铁蛋白和溶菌酶和肌上皮标志物，如S-100蛋白和钙调蛋白呈阳性。这些细胞也表达PLAG 1基因。另一方面，AC细胞仅表达分泌标记物。这些细胞系为研究涎腺肿瘤细胞分化和形态发生的调控机制提供了一种新的体外细胞模型

项目成果

OGAWA, Ikuko: "Pleomorphic adenoma with extensive adenoid cystic carcinoma-like cribriform areas of parotid gland"Pathology International. 53. 30-34 (2003)

OGAWA, Ikuko：“多形性腺瘤，伴有广泛的腺样囊性癌样腮腺筛状区域”国际病理学。

Ogawa, Ikuko: "Dedifferentiated malignant myoepithelioma of the parotid gland"Pathology International. 53. 704-709 (2003)

小川育子：“腮腺去分化恶性肌上皮瘤”国际病理学。

Ogawa L, Miyauchi M., Matsuura H., Takata T.: "Pleomorphic adenoma with extensive adenoid cystic carcinoma-like areas of parotid gland"Pathology International. 53. 30-34 (2003)

Okawa L、Miyauchi M.、Matsuura H.、Takata T.：“腮腺广泛腺样囊性癌样区域的多形性腺瘤”国际病理学。

Ogawa L, Nishida T., Miyauchi M., Sato S., Takata T.: "Dedifferentiated malignant myoepithelioma of the parotid gland"Pathology International. 53. 704-709 (2003)

Okawa L、Nishida T.、Miyauchi M.、Sato S.、Takata T.：“腮腺去分化恶性肌上皮瘤”国际病理学。

小川 郁子: "唾液腺腫瘍の遺伝子異常"病理と臨床. 20. 59-63 (2002)

小川育子：“唾液腺肿瘤的遗传异常”病理学和临床研究 20. 59-63 (2002)。