A role for the E-cadherin cell-cell adhesion molecule during tumor progression of mouse epidermal carcinogenesis.
A role for the E-cadherin cell-cell adhesion molecule during tumor progression of mouse epidermal carcinogenesis.
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DOI：
10.1083/jcb.115.2.517
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发表时间：
1991-10
期刊：
影响因子：
--
通讯作者：
Cano A
中科院分区：
文献类型：
--
作者：
Navarro P;Gómez M;Pizarro A;Gamallo C;Quintanilla M;Cano A
细胞-细胞粘附分子E-和P-钙粘蛋白的表达进行了分析，在7个小鼠表皮角质形成细胞系代表的不同阶段的表皮癌变。已经发现E-钙粘蛋白的量和细胞系的致瘤性之间的负相关性，以及在三种癌细胞系（上皮样HaCa 4和成纤维样CarB和CarC细胞）中完全不存在E-钙粘蛋白的蛋白和mRNA表达。在由细胞系在裸鼠中诱导的肿瘤中检测到类似的结果，其中在由HaCa 4细胞诱导的中度分化的鳞状细胞癌中发生E-钙粘蛋白表达的诱导，尽管其水平比由上皮PDV或PDVC 57细胞系诱导的高度分化的肿瘤低得多。在由CarB或CarC细胞诱导的梭形细胞癌中观察到E-钙粘蛋白表达的完全缺失。在所有表现出上皮（MCA 3D、AT 5、PDV和PDVC 57）或上皮样（HaCa 4）形态的细胞系以及裸鼠肿瘤中均检测到P-钙粘蛋白，与其致瘤能力无关。然而，在成纤维细胞样细胞（CarB和CarC）和梭形细胞癌中观察到完全不存在P-钙粘蛋白。将外源性E-钙粘蛋白cDNA引入HaCa 4细胞，或内源性E-钙粘蛋白基因的再激活，导致这种高度恶性细胞系的致瘤性的部分抑制。这些结果表明，E-钙粘蛋白在小鼠表皮癌发生的恶性进展中的作用。他们还表明，E-和P-钙粘蛋白的丢失可能与癌发生的最后阶段，梭形细胞癌的发展有关。
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.