Azuma M, Fukui K, Yuki T, Tamatani T, Motegi K, Hoque M O, Yoshida H, Sato M
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Japan.
Cancer Lett. 1996 Dec 3;109(1-2):91-9. doi: 10.1016/s0304-3835(96)04430-8.
In this study, we have examined the expression of integrin subunits in normal and malignant human salivary gland cell clones as well as its regulation by transforming growth factor-beta 1 (TGF-beta 1). By the analysis using immunofluorescence staining, an SV40 immortalized normal human salivary gland duct cell clone (NS-SVDC) with no tumorigenic ability by s.c. implantation into nude mice was identified to express the integrin beta 1, alpha 2, alpha 3 and alpha 6 subunits on the cell surface, while the expression of these subunits, except for beta 1 subunit, was reduced or completely diminished in a neoplastic human salivary gland duct cell clone (HSGc) with tumorigenic but not metastatic potential in nude mice and metastatic cell clones derived after in vitro exposure of HSGc to N-methyl-N-nitrosourea. In addition, immunoblot analysis also exhibited the same results as those obtained with immunofluorescence staining. The alpha 1 subunit was not demonstrable in any of the cell clones by both techniques. TGF-beta 1 augmented the expression of the beta 1 subunit in NS-SV-DC, while HSGc and metastatic cell clones demonstrated no changes in the expression of the beta 1 subunit in response to TGF-beta 1. These findings, therefore, suggest that there is an inverse relationship between the malignancy and the expression mode of integrin subunits, especially alpha 2 subunit, in human salivary gland cell clones with varying degrees of malignant potential, and that TGF-beta 1 is a positive regulatory factor in the expression of the beta 1 subunit in normal but not malignant cell clones.
在本研究中，我们检测了整合素亚基在正常和恶性人唾液腺细胞克隆中的表达情况，以及转化生长因子-β1（TGF-β1）对其的调节作用。通过免疫荧光染色分析，鉴定出一株经皮下接种于裸鼠无致瘤能力的SV40永生化正常人唾液腺导管细胞克隆（NS-SVDC）在细胞表面表达整合素β1、α2、α3和α6亚基，而在一株在裸鼠中有致瘤但无转移潜能的人唾液腺导管肿瘤细胞克隆（HSGc）以及HSGc体外暴露于N-甲基-N-亚硝基脲后获得的转移细胞克隆中，除β1亚基外，这些亚基的表达减少或完全消失。此外，免疫印迹分析也得到了与免疫荧光染色相同的结果。两种技术在任何细胞克隆中均未检测到α1亚基。TGF-β1增强了NS-SV-DC中β1亚基的表达，而HSGc和转移细胞克隆对TGF-β1刺激下β1亚基的表达无变化。因此，这些发现表明，在具有不同程度恶性潜能的人唾液腺细胞克隆中，恶性程度与整合素亚基尤其是α2亚基的表达模式呈负相关，并且TGF-β1是正常而非恶性细胞克隆中β1亚基表达的正调节因子。
