EPITHELIAL-STROMAL DIALOGUE IN BREAST CANCER: IMPLICATIONS FOR CELL ADHESION

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 differentiated 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 nuclear 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 significantly 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