Angelucci, Cristiana

Fabbri, Cristina

Lama, Gina

Masetti, Riccardo

Maulucci, Giuseppe

Proietti, Gabriella

Sica, Gigliola

Firenze University Press: E-Journals

IJAE Vol. 115, n. 1/2 (Supplement), 2010
12
Epithelial-stromal dialogue in breast cancer: 
implications for cell adhesion
Cristiana Angelucci1, Gina Lama1, Gabriella Proietti1, Cristina Fabbri2, Giuseppe Maulucci3, Riccardo 
Masetti2 and Gigliola Sica1
1 Institute of Histology and Embryology, Faculty of Medicine “A. Gemelli”, Catholic University of the Sacred Heart, 
Rome, Italy
2 Department of Surgery, Breast Unit, Faculty of Medicine “A. Gemelli”, Catholic University of the Sacred Heart, Rome, 
Italy
3 Institute of Physics, Faculty of Medicine “A. Gemelli”, Catholic University of the Sacred Heart, Rome, Italy
Stromal fibroblasts have been reported to interfere with proliferation and invasion of 
cancer cells. Our objective was to elucidate, using a three-dimensional coculture system 
(nodules), the interaction between a human, estrogen receptor-positive, well differenti-
ated breast cancer cell line (MCF-7) and fibroblasts isolated from breast healthy skin 
(normal fibroblasts, NFs) or from breast tumor stroma (cancer associated fibroblasts, 
CAFs) in terms of cell growth and adhesion. The cell proliferating fraction of each cell 
type was evaluated by immunohistochemical detection of two cell cycle-associated nu-
clear proteins: Ki67 and proliferating cell nuclear antigen (PCNA). The expression of 
epithelial adhesion molecule E-cadherin was investigated in MCF-7 cells by confocal 
immunofluorescence microscopy. The MCF-7 cells/CAFs mixed nodules showed a sig-
nificantly larger proportion (50%, p<0.001, Tukey’s multiple comparison test) of Ki67-
positive tumor cells with respect to that observed in MCF-7cells/NFs (30.6%, p<0.001) 
or MCF-7 (34.8%, p<0.001) nodules. MCF-7 cells seemed to have no influence on the 
growth of both kinds of fibroblasts. Similar results were obtained with PCNA, even 
though a more heterogeneous and less intense nuclear staining was observed. Immuno-
fluorescence analysis showed that in MCF-7 cells/NFs nodules E-cadherin expression 
level in tumor cells was about 2.5 fold higher than that observed in MCF-7 cultured 
alone and about 16 fold higher than that showed by MCF-7 cells cocultured with CAFs. 
These data support the hypothesis that the activated fibroblasts residing in the breast 
tumor stroma are able to transmit mitogenic signals to the epithelial cancer cells. Con-
cerning cell adhesion, our results clearly demonstrate the ability of CAFs to negatively 
affect cell-cell contacts of epithelial cells by strongly reducing E-cadherin expression. 
The crosstalk of tumor cells with NFs seems to play a crucial role in preventing disrup-
tion of cell junctions, cell shape changes and migration.
Key words
Epithelium, stroma, breast cancer, cell growth, adhesion, E-cadherin


Epithelial-stromal dialogue in breast cancer: implications for cell adhesion

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Epithelial-stromal dialogue in breast cancer: implications for cell adhesion

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