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Carcinogenesis Advance Access published online on June 23, 2005
Carcinogenesis, doi:10.1093/carcin/bgi158
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received December 17, 2004
Revised June 10, 2005
Accepted June 15, 2005

CANCER BIOLOGY

Mammary carcinoma provides highly tumourigenic and invasive reactive stromal cells

Mirco Galiè 1*, Carlo Sorrentino 2, Maura Montani 3, Luigi Micossi 3, Emma Di Carlo 2, Tommaso D'Antuono 2, Laura Calderan 1, Pasquina Marzola 1, Donatella Benati 1, Flavia Merigo 1, Fiorenza Orlando 4, Arianna Smorlesi 4, Cristina Marchini 3, Augusto Amici 3, and Andrea Sbarbati 1

1 Dept. Morphological and Biomedical Sciences, Sec. Anatomy and Histology, University of Verona, Verona (VR) (Italy)
2 Dept. Oncology and Neuroscience, Sec. Surgical Pathology, University of Chieti, Chieti (CH) (Italy)
3 Dept. Molecular, Cellular and Animal Biology, Genetic Immunization laboratory, University of Camerino, Camerino (MC) (Italy)
4 Dept. INRCA Gerontology Research, Immunology Center, Ancona (Italy)

* To whom correspondence should be addressed.
Mirco Galiè, E-mail: mirco{at}anatomy.univr.it


  Abstract

The progression of a lesion to 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 gland. 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-SMA at the invasive edge. The expression of cytokeratin 14 suggested a myopepithelial 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 tumorigenic 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.


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