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

1.细胞黏附分子E-cad、α，β-catenin、CD44v6和v9在正常涎腺和无肌上皮参与的涎腺肿瘤细胞膜上表达较强，而在多形性腺瘤(PA)中即使在实体增生区表达强度也较低。在腺样囊性癌中，E-钙粘蛋白和β-连环蛋白表达于细胞膜上，但分布不规则，有微小斑点状沉积。在少数癌组织中，β-连环蛋白存在于细胞核中，提示它可能在癌的发生发展中起一定作用。另一方面，CD44变异体的低表达可能与ACC2的转移潜能无关。在E-钙粘附素表达降低和β-连环蛋白核表达降低的癌组织中，可检测到表皮生长因子受体的过度表达，提示表皮生长因子受体途径可能通过WINT信号转导途径促进多种基因的表达。ACC细胞外基质中含有基质金属蛋白酶-2和-9，可能在破坏基底膜和肿瘤细胞的侵袭转移中发挥重要作用。通过转导hTERT基因获得永生化的PA和腺泡细胞癌(AC)细胞系。永生化的PA细胞既有乳铁蛋白、溶菌酶等分泌标志物阳性，也有S-100蛋白、钙蛋白等肌上皮标志物阳性。这些细胞也表达PLAG1基因。而AC细胞仅表达分泌标志物。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。

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