Epithelial-mesenchymal interactions in breast cancer: evidence for a role of nuclear localized β-catenin in carcinoma-associated fibroblasts.
OBJECTIVE
Characteristics of the stroma around tumours are critical in defining the behaviour of cancers. β-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 β-catenin within the stromal fibroblasts of breast cancer.


RESULTS
We examined β-catenin expression in 201 breast cancers and adjacent normal tissue. Fibroblasts expressing nuclear β-catenin were present in a significantly greater proportion of tumour tissues than normal tissues. The presence of fibroblasts with nuclear β-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 β-catenin, showed fibroblasts transfected to allow overexpression of β-catenin were capable of inducing increases in both proliferation and invasion of breast cancer cell lines.


CONCLUSIONS
The presence of fibroblasts with nuclear β-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.
Department of Histopathology, Leeds Teaching Hospital NHS Trust, Leeds, UK.
Eldo T
ET
Verghese
Hrishikesh
H
Shenoy
Victoria J
VJ
Cookson
Caroline A
CA
Green
Jo
J
Howarth
R H
RH
Partanen
Steven
S
Pollock
Alison
A
Waterworth
Valerie
V
Speirs
Thomas A
TA
Hughes
Andrew M
AM
Hanby
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D014162:Transfection; D059016:Tumor Microenvironment / Q000502:physiology*; D051176:beta Catenin / Q000032:analysis / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051176:beta Catenin