Navarro P, Gómez M, Pizarro A, Gamallo C, Quintanilla M, Cano A
Departamento de Bioquímica, Facultad Medicina, Universidad Autónoma de Madrid, Spain.
J Cell Biol. 1991 Oct;115(2):517-33. doi: 10.1083/jcb.115.2.517.
The expression of the cell-cell adhesion molecules E- and P-cadherin has been analyzed in seven mouse epidermal keratinocyte cell lines representative of different stages of epidermal carcinogenesis. An inverse correlation between the amount of E-cadherin protein and tumorigenicity of the cell lines has been found, together with a complete absence of E-cadherin protein and mRNA expression in three carcinoma cell lines (the epithelioid HaCa4 and the fibroblastoid CarB and CarC cells). A similar result has been detected in tumors induced in nude mice by the cell lines, where induction of E-cadherin expression takes place in moderately differentiated squamous cell carcinomas induced by HaCa4 cells, although at much lower levels than in well-differentiated tumors induced by the epithelial PDV or PDVC57 cell lines. Complete absence of E-cadherin expression has been observed in spindle cell carcinomas induced by CarB or CarC cells. P-cadherin protein was detected in all cell lines that exhibit an epithelial (MCA3D, AT5, PDV, and PDVC57) or epithelioid (HaCa4) morphology, as well as in nude mouse tumors, independent of their tumorigenic capabilities. However, complete absence of P-cadherin was observed in the fibroblast-like cells (CarB and CarC) and in spindle cell carcinomas. The introduction of an exogenous E-cadherin cDNA into HaCa4 cells, or reactivation of the endogenous E-cadherin gene, leads to a partial suppression of the tumorigenicity of this highly malignant cell line. These results suggest a role for E-cadherin in the progression to malignancy of mouse epidermal carcinogenesis. They also suggest that the loss of both E- and P-cadherin could be associated to the final stage of carcinogenesis, the development of spindle cell carcinomas.
在代表表皮癌发生不同阶段的七种小鼠表皮角质形成细胞系中，分析了细胞间粘附分子E -钙粘蛋白和P -钙粘蛋白的表达情况。已发现细胞系中E -钙粘蛋白蛋白的量与致瘤性呈负相关，并且在三种癌细胞系（上皮样的HaCa4和成纤维细胞样的CarB和CarC细胞）中完全不存在E -钙粘蛋白蛋白和mRNA表达。在用这些细胞系诱导裸鼠产生的肿瘤中也检测到了类似结果，其中在HaCa4细胞诱导的中度分化鳞状细胞癌中发生了E -钙粘蛋白表达的诱导，尽管其水平远低于上皮性PDV或PDVC57细胞系诱导的高分化肿瘤。在CarB或CarC细胞诱导的梭形细胞癌中观察到E -钙粘蛋白表达完全缺失。在所有呈现上皮形态（MCA3D、AT5、PDV和PDVC57）或上皮样形态（HaCa4）的细胞系以及裸鼠肿瘤中均检测到了P -钙粘蛋白蛋白，与它们的致瘤能力无关。然而，在成纤维细胞样细胞（CarB和CarC）和梭形细胞癌中观察到P -钙粘蛋白完全缺失。将外源性E -钙粘蛋白cDNA导入HaCa4细胞，或使内源性E -钙粘蛋白基因重新激活，导致这种高度恶性细胞系的致瘤性部分受到抑制。这些结果表明E -钙粘蛋白在小鼠表皮癌发生发展为恶性肿瘤的过程中发挥作用。它们还表明E -钙粘蛋白和P -钙粘蛋白的缺失可能与癌发生的最后阶段，即梭形细胞癌的发展有关。
