Fig. 7
From: LOX-catalyzed collagen stabilization is a proximal cause for intrinsic resistance to chemotherapy
Hypoxia sensitivity and reliance on FAK signaling controls response toward LOX(L)-inhibition. a IHC staining for Ki-67 shows that changes in proliferating cell density correlate with the effects on growth rate by LOX(L) inhibition (n = 6–10). b Regional differences in Ki-67 staining in LLC tumors. In the central region of the tumor density of proliferating cells is significantly lower than in the highly proliferative rim region (SB = 1000 µm). c Spatial resolution of Ki-67 staining intensity in βAPN-treated and control LLC tumors, following trajectories from the tumors’ outer margins to the center (n = 4). d Relative proliferation rate of murine tumor cells on substrates with variable stiffness (n = 3). e Effect of FAK inhibition and reduced oxygen supply on tumor cell proliferation and viability in cell culture. EC50 values of FAK inhibitor PF-573,228 in various cell lines. Selected threshold value defining sensitivity to PF-573,228 (EC50 < 500 nM) is indicated. (n = 3). Doubling time (Td) of tumor cells at reduced oxygen levels (2% O2) (n = 5). Error bars: ±SEM. * indicates statistical significance vs. control, *P < 0.05, **P < 0.01, ***P < 0.001
