Tumour-stroma interactions in colorectal cancer: converging on beta-catenin activation and cancer stemness

Abstract

Sporadic cases of colorectal cancer are primarily initiated by gene mutations in members of the canonical Wnt pathway, ultimately resulting in beta-catenin stabilisation. Nevertheless, cells displaying nuclear beta-catenin accumulation are nonrandomly distributed throughout the tumour mass and preferentially localise along the invasive front where parenchymal cells are in direct contact with the stromal microenvironment. Here, we discuss the putative role played by stromal cell types in regulating beta-catenin intracellular accumulation in a paracrine fashion. As such, the tumour microenvironment is likely to maintain the cancer stem cell phenotype in a subset of cells, thus mediating invasion and metastasis.

Figure 1

β-Catenin immunohistochemical staining of formalin-fixed, paraffin-embedded normal human colonic epithelia (panels A and B), and of a primary colorectal tumour (panels C and D) and a liver metastasis (panels E and F). The right panels contain magnifications (× 40) of specific areas from the left panels (× 20). The arrowheads in panels A and B indicate an epithelial cell localised at the base of the crypt with nuclear β-catenin accumulation. Both the primary colorectal tumour and liver metastasis (panels C–F) show nuclear β-catenin accumulation in cells invading the surrounding stroma, whereas other tumour cells display only membranous localisation.