Epithelial-mesenchymal interactions in breast cancer: evidence for a role of nuclear localized β-catenin in carcinoma-associated fibroblasts

Aims: Characteristics of the stroma around tumours are critical in defining the behaviour of cancers. beta-Catenin is well established as a critical regulator of carcinogenesis, acting as a transcriptional co-activator in the nuclei of epithelial cancer cells. We have examined the prevalence and influence of nuclear beta-catenin within the stromal fibroblasts of breast cancer. Methods and results: We examined beta-catenin expression in 201 breast cancers and adjacent normal tissue. Fibroblasts expressing nuclear beta-catenin were present in a significantly greater proportion of tumour tissues than normal tissues. The presence of fibroblasts with nuclear beta-catenin in tumours correlated with survival; tumours with prevalent positive fibroblasts were associated significantly with relatively good prognoses. Functional studies to examine influences of fibroblasts with nuclear beta-catenin, showed fibroblasts transfected to allow overexpression of beta-catenin were capable of inducing increases in both proliferation and invasion of breast cancer cell lines. Conclusion: The presence of fibroblasts with nuclear beta-catenin in tumours is a good prognostic indicator, although in the context of tissue culture models these cells can increase the growth and metastatic potential of cancer cells. These apparently paradoxical observations underline the complexity of epithelial-stromal signalling within tumours and highlight an area for further study.