Caulín C, Bauluz C, Gandarillas A, Cano A, Quintanilla M
Departamento de Bioquimica, Facultad de Medicina UAM, Madrid, Spain.
Exp Cell Res. 1993 Jan;204(1):11-21. doi: 10.1006/excr.1993.1003.
We have studied in this report the expression of keratins in mouse epidermal keratinocytes transformed in culture by a chemical carcinogen (PDV) and in cell lines (PDVCM1, PDVCM2, PDVCV1, and PDVC57) derived by tumor transplantation of PDV cells in syngeneic C57Bl/6 mice. PDV, PDVCM1, PDVCM2, and PDVCV1 cell lines are weakly to moderately tumorigenic, giving rise to squamous cell carcinomas, although not at all injection points, whereas PDVC57 cells are more malignant, inducing highly anaplastic carcinomas at 100% of injection sites. All the cell lines synthesize anomalously simple epithelial keratins, substantial amounts of K8, and minor quantities of K18 and K19, but the level of expression is increased in PDVC57. We have found that in PDVC57 cells upregulation of K8 is linked to down-regulation of the normal keratins produced by epidermal keratinocytes in culture (i.e., K5, K6, K14, and K17). On the other hand, K8 does not generally colocalize with K13, a keratin also aberrantly expressed by epidermal cell cultures when induced to differentiate by high Ca2+ medium. K13, normally synthesized in internal stratified epithelia, is anomalously induced in mouse epidermal tumors and has been used as an early marker of carcinoma progression. In tumors induced by the cell lines upon injection in mice, K8 is found in the less differentiated regions as opposite to K13, restricted to the differentiating areas of the tumors. In PDV, PDVCM1, PDVCM2, and PDVCV1 carcinomas the overall expression of K13 is higher than that of K8. However, this relation is inverted in tumors induced by PDVC57 cells, in a good correlation with the tumoral phenotypes produced by the cell lines. Our results suggest that upregulation of the simple epithelial keratin K8, as found in transformed epidermal cell lines and tumors, is a late marker of malignant progression and is associated with the loss of the differentiated phenotype.
在本报告中，我们研究了化学致癌物（PDV）在培养中转化的小鼠表皮角质形成细胞以及通过将PDV细胞移植到同基因C57Bl/6小鼠中获得的细胞系（PDVCM1、PDVCM2、PDVCV1和PDVC57）中角蛋白的表达情况。PDV、PDVCM1、PDVCM2和PDVCV1细胞系具有弱至中度致瘤性，可引发鳞状细胞癌，不过并非在所有注射部位都会发生，而PDVC57细胞的恶性程度更高，在100%的注射部位诱导产生高度间变的癌。所有细胞系均异常合成简单的上皮角蛋白，大量表达K8，少量表达K18和K19，但在PDVC57中表达水平有所升高。我们发现，在PDVC57细胞中，K8的上调与培养的表皮角质形成细胞产生的正常角蛋白（即K5、K6、K14和K17）的下调相关。另一方面，K8通常不与K13共定位，K13是表皮细胞培养物在高钙培养基诱导分化时也异常表达的一种角蛋白。K13通常在内层复层上皮中合成，在小鼠表皮肿瘤中异常诱导表达，并已被用作癌进展的早期标志物。在细胞系注射到小鼠体内诱导产生的肿瘤中，K8存在于分化程度较低的区域，与K13相反，K13局限于肿瘤的分化区域。在PDV、PDVCM1、PDVCM2和PDVCV1癌中，K13的总体表达高于K8。然而，在PDVC57细胞诱导产生的肿瘤中这种关系则相反，这与细胞系产生的肿瘤表型具有良好的相关性。我们的结果表明，在转化的表皮细胞系和肿瘤中发现的简单上皮角蛋白K8的上调是恶性进展的晚期标志物，并且与分化表型的丧失相关。
