Cadherin-23 mediates heterotypic cell-cell adhesion between breast cancer epithelial cells and fibroblasts

In the early stages of breast cancer metastasis, epithelial cells penetrate the basement membrane and invade the surrounding stroma, where they encounter fibroblasts. Paracrine signaling between fibroblasts and epithelial tumor cells contributes to the metastatic cascade, but little is known about t...

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Bibliographic Details
Published in:PloS one 2012-03, Vol.7 (3), p.e33289-e33289
Main Authors: Apostolopoulou, Maria, Ligon, Lee
Format: Article
Language:English
Subjects:
Adhesion
Antibodies
Biology
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cadherins
Cadherins - genetics
Cadherins - metabolism
Cancer
Cancer metastasis
Cell adhesion
Cell adhesion & migration
Cell Adhesion - genetics
Cell culture
Cell growth
Cell Line
Epithelial cells
Epithelial Cells - metabolism
Female
Fibroblasts
Fibroblasts - metabolism
Gene Expression
Gene Expression Regulation, Neoplastic
Humans
Immunoblotting
Immunocytochemistry
Interdisciplinary aspects
Kinases
Medicine
Melanoma
Metastases
Metastasis
Paracrine signalling
Protein Transport
Proteins
RNA-mediated interference
Stroma
Tumor cells
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Summary:In the early stages of breast cancer metastasis, epithelial cells penetrate the basement membrane and invade the surrounding stroma, where they encounter fibroblasts. Paracrine signaling between fibroblasts and epithelial tumor cells contributes to the metastatic cascade, but little is known about the role of adhesive contacts between these two cell types in metastasis. Here we show that MCF-7 breast cancer epithelial cells and normal breast fibroblasts form heterotypic adhesions when grown together in co-culture, as evidenced by adhesion assays. PCR and immunoblotting show that both cell types express multiple members of the cadherin superfamily, including the atypical cadherin, cadherin-23, when grown in isolation and in co-culture. Immunocytochemistry experiments show that cadherin-23 localizes to homotypic adhesions between MCF-7 cells and also to heterotypic adhesions between the epithelial cells and fibroblasts, and antibody inhibition and RNAi experiments show that cadherin-23 plays a role in mediating these adhesive interactions. Finally, we show that cadherin-23 is upregulated in breast cancer tissue samples, and we hypothesize that heterotypic adhesions mediated by this atypical cadherin may play a role in the early stages of metastasis.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0033289