Journal Article

Mammary carcinoma provides highly tumourigenic and invasive reactive stromal cells

Mirco Galiè, Carlo Sorrentino, Maura Montani, Luigi Micossi, Emma Di Carlo, Tommaso D'Antuono, Laura Calderan, Pasquina Marzola, Donatella Benati, Flavia Merigo, Fiorenza Orlando, Arianna Smorlesi, Cristina Marchini, Augusto Amici and Andrea Sbarbati

in Carcinogenesis

Volume 26, issue 11, pages 1868-1878
Published in print November 2005 | ISSN: 0143-3334
Published online June 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi158
Mammary carcinoma provides highly tumourigenic and invasive reactive stromal cells

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The progression of a lesion to a carcinoma is dependent on the engagement of ‘reactive stroma’ that provides structural and vascular support for tumour growth and also leads to tissue reorganization and invasiveness. The composition of reactive stroma closely resembles that of granulation tissue, and myofibroblasts are thought to play a critical role in driving the stromal reaction of invasive tumours as well as of physiological wound repair. In the present work, we established a myofibroblast-like cell line, named A17, from a mouse mammary carcinoma model in which tumourigenesis is triggered in a single step by the overexpression of HER-2/neu transgene in the epithelial compartment of mammary glands. We showed that although they derived from a tumour of epithelial origin and did not express HER-2/neu transgene, their subcutaneous injection into the backs of syngeneic mice gave rise to sarcomatoid tumours which expressed alpha-smooth muscle actin at the invasive edge. The expression of cytokeratin 14 suggested a myoepithelial origin but immunophenotypical profile, invasive and neoangiogenic potential of A17 cells and tumours showed many similarities with the reactive stroma that occurs in wound repair and in cancerogenesis. Our results suggest that epithelial tumours have the potential to develop highly tumourigenic and invasive reactive stromal cells and our cell line represents a novel, effective model for studying epithelial-stromal interaction and the role of myofibroblasts in tumour development.

Keywords: alpha-SMA, alpha-smooth muscle actin; bFGF, basic fibroblast growth factor; DCE-MRI, dynamic contrast enhanced magnetic resonance imaging; EMT, epithelial–mesenchymal transition; fPV, fractional plasma volume; IL-6, interleukin-6; Kps, endothelial transfer coefficient; PCNA, proliferating cell nuclear antigen; PDGF-A, platelet derived growth factor-A; TGF-beta, transforming growth factor beta; VEGF, vascular endothelial growth factor

Journal Article.  7665 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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