Sugiyama M, Speight P M, Prime S S, Watt F M
Keratinocyte Laboratory, Imperial Cancer Research Fund, London, UK.
Carcinogenesis. 1993 Oct;14(10):2171-6. doi: 10.1093/carcin/14.10.2171.
Receptors of the integrin family regulate adhesion and terminal differentiation of keratinocytes. In order to investigate the significance of changes in integrin expression associated with malignant transformation we have examined normal human oral keratinocytes and seven oral squamous cell carcinoma (SCC) lines. Cell surface levels of the alpha 2, alpha 3, alpha 5, alpha 6, alpha v, beta 1 and beta 4 integrin subunits were determined by flow cytometry and the distribution of the beta 1 subunit was examined by immunohistochemistry. In normal keratinocytes and one SCC line the beta 1 subunit was most abundant in the basal cell layer, but in other lines anti-beta 1 antibodies stained basal and suprabasal layers uniformly. All lines had reduced surface levels of at least one integrin subunit and in some cell lines distinct subpopulations could be distinguished on the basis of differences in integrin expression. Reduced integrin expression was not, however, generally reflected in reduced adhesion to laminin, fibronectin, type IV collagen or vitronectin in three cell lines examined. Those cell lines with the lowest capacity for terminal differentiation, as measured by involucrin expression, had the lowest levels of the alpha 6 and beta 4 subunits or were completely lacking alpha v. Oral SCC show considerable variation in integrin expression, but focal or extensive loss of the alpha 6 and beta 4 subunits is a common feature of poorly differentiated tumours. The cell lines we have examined therefore provide a relevant experimental model with which to explore the relationship between aberrant integrin expression and impaired terminal differentiation capacity.
整合素家族的受体调节角质形成细胞的黏附及终末分化。为了研究与恶性转化相关的整合素表达变化的意义，我们检测了正常人口腔角质形成细胞和7种口腔鳞状细胞癌（SCC）细胞系。通过流式细胞术测定α2、α3、α5、α6、αv、β1和β4整合素亚基的细胞表面水平，并通过免疫组织化学检测β1亚基的分布。在正常角质形成细胞和一种SCC细胞系中，β1亚基在基底细胞层中最为丰富，但在其他细胞系中，抗β1抗体均匀地染色基底和基底上层。所有细胞系至少有一种整合素亚基的表面水平降低，并且在一些细胞系中，基于整合素表达的差异可以区分出不同的亚群。然而，在所检测的三种细胞系中，整合素表达降低通常并未反映在对层粘连蛋白、纤连蛋白、IV型胶原或玻连蛋白的黏附能力降低上。通过内聚蛋白表达测定，那些终末分化能力最低的细胞系，其α6和β4亚基水平最低或完全缺乏αv。口腔SCC在整合素表达上表现出相当大的差异，但α6和β4亚基的局灶性或广泛性缺失是低分化肿瘤的一个共同特征。因此，我们检测的细胞系提供了一个相关的实验模型，用以探索异常整合素表达与终末分化能力受损之间的关系。
