Mammary carcinoma provides highly tumourigenic and invasive reactive stromal cells.
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.
Galiè
Mirco
M
Department of Morphological and Biomedical Sciences, Section Anatomy and Histology, University of Verona, Verona, Italy. mirco@anatomy.univr.it
Sorrentino
Carlo
C
Montani
Maura
M
Micossi
Luigi
L
Di Carlo
Emma
E
D'Antuono
Tommaso
T
Calderan
Laura
L
Marzola
Pasquina
P
Benati
Donatella
D
Merigo
Flavia
F
Orlando
Fiorenza
F
Smorlesi
Arianna
A
Marchini
Cristina
C
Amici
Augusto
A
Sbarbati
Andrea
A
D000818:Animals; D015153:Blotting, Western; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D009682:Magnetic Resonance Spectroscopy; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness / Q000473:pathology*; D016133:Polymerase Chain Reaction; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012192:Retroviridae Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012509:Sarcoma / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D018719:Erb-b2 Receptor Tyrosine Kinases; D016212:Transforming Growth Factor beta