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

Invasion and dissemination of well-differentiated carcinomas are often asso ciated with loss of epithelial differentiation and gain of mesenchyme-like capabilities of the tumor cells at the invasive front. However, when compar ing central areas of primary colorectal carcinomas and corresponding metast ases, we again found the same differentiated epithelial growth patterns. Th ese characteristic phenotypic changes were associated with distinct express ion patterns of beta -catenin, the main oncogenic protein in colorectal car cinomas, and E-cadherin. Nuclear beta -catenin was found in dedifferentiate d mesenchyme-like tumor cells at the invasive front, but strikingly, as in central areas of the primary tumors, was localized to the membrane and cyto plasm in polarized epithelial tumor cells in the metastases. This expressio n pattern was accompanied by changes in E-cadherin expression and prolifera tive activity. On the basis of these data, we postulate that an important d riving force for progression of well-differentiated colorectal carcinomas i s the specific environment, initiating two transient phenotypic transition processes by modulating intracellular beta -catenin distribution in tumor c ells.