Tumor - stroma interactions alter the sensitivity of drug in breast cancer

Flat cell cultures or xenografts are inadequate tools to unravel cancer complex biology.
3D in vitro tumor models garnered interest since they recapitulate better dynamic
mechanisms of cancer, but a gold standardmodel that faithfullymimics solid cancer is not
available yet. 3D breast cancermodel is fabricated using freeze-dried silk fibroin scaffolds.
Breast cancer cell lines (MCF-7 and MDA-MB231) are seeded with normal mammary
fibroblasts onto silk fibroin scaffold (1 and 2mm thick). Cells proliferation is monitored
by means of Alamar blue assay. 3D breast cancer models morphology is observed
by confocal microscopy. Gene expression modulation concerning extracellular matrix
markers is evaluated. Further, 3D bioengineered breast cancer models are treated with
doxorubicin. Silk fibroin scaffolds allow the proliferation of cancer cells and fibroblasts.
Cells growth is enhanced when cancer cells and fibroblasts are seeded together.
Histological staining shows 3D cell organization. MMP-1, MMP-2, MMP-3, Col-1, and
Fibronectin expression is upregulated in co-culture. After doxorubicin treatment, stronger
reduction in cell activity is observed in 2mm SF scaffold in comparison to 1mm. The
3D in vitro breast cancer model obtained can easily be scaled-up and translated to the
preclinical testing of novel chemotherapeutics.