Figure 5

Effect of inhibitors on fibroblast-induced co-unit disruption. (a) Cultures were generated with MCF-7 cells, myoepithelial cells and tumour-associated fibroblasts (TAFs) without prior aggregation, and grown in the (a)i,ii presence of dimethyl sulfoxide (DMSO) (10 μM), a specific inhibitor for c-met, (a)iii,iv the receptor for HGF, (PHA 665752, 100 nM), (a)iv,vii a broad spectrum matrix metalloproteinase (MMP) inhibitor (10 μM) individually, or (a)vii,viii in combination. Inhibitors were replenished at two-day intervals and the cultures harvested at seven days. (b) In the vehicle control cultures exhibited an average of two co-units per microscopic field. This was significantly increased in the presence of the c-met inhibitor (average co-units 4.6, p = 0.016), the MMP inhibitor (average co-units 7, p ≤ 0.001) and the inhibitors in combination (average co-units 7.5, p = 0.001).