Variable β-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment
Variable β-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment
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DOI：
10.1073/pnas.171610498
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发表时间：
2001-08-28
影响因子：
11.1
通讯作者：
Kirchner, T
中科院分区：
文献类型：
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作者：
Brabletz, T;Jung, A;Kirchner, T
高分化癌的侵袭和传播通常与上皮分化的丧失和肿瘤细胞在侵袭前沿的间质样能力的获得有关。然而，当比较原发性结直肠癌的中心区域和相应的转移灶时，我们再次发现相同的分化上皮生长模式。这些特征性的表型变化与结直肠癌中主要的致癌蛋白- β -catenin和E-cadherin的不同表达模式有关。核β -连环蛋白在侵袭前的去分化间质样肿瘤细胞中被发现，但在转移的极化上皮肿瘤细胞中，与原发肿瘤的中心区域一样，引人注目地定位于膜和细胞质。这种表达模式伴随着E-cadherin表达和增殖活性的变化。基于这些数据，我们假设高分化结直肠癌进展的重要驱动力是特定环境，通过调节肿瘤细胞内β -catenin分布启动两个短暂的表型转变过程。
Invasion and dissemination of well-differentiated carcinomas are often associated with loss of epithelial differentiation and gain of mesenchyme-like capabilities of the tumor cells at the invasive front. However, when comparing central areas of primary colorectal carcinomas and corresponding metastases, we again found the same differentiated epithelial growth patterns. These characteristic phenotypic changes were associated with distinct expression patterns of beta -catenin, the main oncogenic protein in colorectal carcinomas, and E-cadherin. Nuclear beta -catenin was found in dedifferentiated mesenchyme-like tumor cells at the invasive front, but strikingly, as in central areas of the primary tumors, was localized to the membrane and cytoplasm in polarized epithelial tumor cells in the metastases. This expression pattern was accompanied by changes in E-cadherin expression and proliferative activity. On the basis of these data, we postulate that an important driving force for progression of well-differentiated colorectal carcinomas is the specific environment, initiating two transient phenotypic transition processes by modulating intracellular beta -catenin distribution in tumor cells.