Variable β-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment

T Brabletz, A Jung, S Reu, M Porzner… - Proceedings of the …, 2001 - National Acad Sciences
T Brabletz, A Jung, S Reu, M Porzner, F Hlubek, LA Kunz-Schughart, R Knuechel, T Kirchner
Proceedings of the National Academy of Sciences, 2001National Acad Sciences
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 β-catenin, the main oncogenic protein in colorectal carcinomas, and E-cadherin …
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 β-catenin, the main oncogenic protein in colorectal carcinomas, and E-cadherin. Nuclear β-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 β-catenin distribution in tumor cells.
National Acad Sciences