Bagutti C, Speight P M, Watt F M
Keratinocyte Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, U.K.
J Pathol. 1998 Sep;186(1):8-16. doi: 10.1002/(SICI)1096-9896(199809)186:1<8::AID-PATH156>3.0.CO;2-H.
In addition to their role in maintenance of tissue integrity, cell adhesion molecules regulate the growth and differentiation of stratified squamous epithelia. Reduced expression of E-cadherin and the alpha 2 beta 1, alpha 3 beta 1 and alpha 6 beta 4 integrins is already reported to correlate with poor histological differentiation in oral squamous cell carcinomas. However, it is not clear how closely cadherin and integrin loss are related in any given tumour, nor whether cadherin loss is correlated with changes in expression of the cytoplasmic regulatory proteins known as catenins. Double-label immunofluorescence has been used to stain a panel of 22 oral squamous cell carcinomas with antibodies to ten proteins, including E- and P-cadherin, the major keratinocyte integrin subunits, and alpha-, beta- and gamma-catenin. Overall, E-cadherin expression and integrin expression correlated well with tumour grade, while P-cadherin staining was more variable. All tumours, regardless of differentiation status, showed reduced staining for at least two of the catenins, implying that the adhesive function of E- and P-cadherin could be impaired even when cadherin expression is normal. It is concluded that in all squamous cell carcinomas, regardless of degree of histological differentiation, there is some perturbed expression of cell adhesion molecules and that integrin and E-cadherin loss are closely related.
除了在维持组织完整性方面发挥作用外,细胞粘附分子还调节复层鳞状上皮的生长和分化。据报道,E-钙粘蛋白以及α2β1、α3β1和α6β4整合素的表达降低与口腔鳞状细胞癌的组织学分化差相关。然而,在任何给定肿瘤中,钙粘蛋白和整合素缺失之间的关联程度尚不清楚,钙粘蛋白缺失是否与称为连环蛋白的细胞质调节蛋白表达的变化相关也不清楚。双标记免疫荧光已用于用针对十种蛋白质的抗体对一组22例口腔鳞状细胞癌进行染色,这些蛋白质包括E-钙粘蛋白和P-钙粘蛋白、主要的角质形成细胞整合素亚基以及α-、β-和γ-连环蛋白。总体而言,E-钙粘蛋白表达和整合素表达与肿瘤分级密切相关,而P-钙粘蛋白染色变化更大。所有肿瘤,无论分化状态如何,至少两种连环蛋白的染色均减少,这意味着即使钙粘蛋白表达正常,E-钙粘蛋白和P-钙粘蛋白的粘附功能也可能受损。得出的结论是,在所有鳞状细胞癌中,无论组织学分化程度如何,细胞粘附分子的表达都存在一些紊乱,并且整合素和E-钙粘蛋白的缺失密切相关。