Fig. 8.

Inhibiting MMP activity increases cancer cell migration through collagen microtracks. (A) Rose plot shows trajectories of MDAMB231 metastatic breast cancer cells migrating within a fully 3D collagen matrix and (B) in collagen tracks over 100 minutes. (C) Rose plots show that treatment with GM6001, a broad spectrum MMP inhibitor, decreases invasion in 3D, but (D) increases invasion within the collagen tracks. Note that the trajectories in (B) and (D) have been arbitrarily rotated for a more direct visual comparison to (A) and (C). (E) Quantification of speed indicates that treatment with GM6001 has no effect on speed in a fully 3D matrix, but increases the speed of cells within the microtracks. Additionally, treatment with a structural analog of GM6001 (NC-GM6001) has no significant effect on speed in 3D matrices or microtracks. Mean + SD; * indicates p < 0.05; n > 30 cells, 3 independent experiments. (F) GM6001 treatment of cells migrating on 2D glass substrates has no effect on cell speed. Mean + SD; n > 40 cells, 1 independent experiment. (G) Treatment of cells with other broad spectrum inhibitors (BB2516 and a commercial protease inhibitor cocktail) has no effect on cell speed in the tracks. Mean + SD; n > 60 cells, 2 independent experiments. (H) Similarly, inhibiting MT1-MMP with siRNA significantly decreases speed in 3D matrices, but has no effect within tracks. Mean + SD; * indicates p < 0.05; n > 30 cells, 2 independent experiments.