Skip to main content
. 2019 Aug 1;3(1):e1209. doi: 10.1002/cnr2.1209

Figure 4.

Figure 4

Targeting CAFs and stromal remodelling. A, Cancer associated fibroblasts derived from two matched models, the tumourigenic and highly invasive KPC (KPC‐CAFs), and the tumourigenic but poorly invasive KPflC (KPCfl‐CAFs) models of pancreatic ductal adenocarcinoma show differences in their ability to remodel the Mini‐Organos [2.5 mg/mL Col I] reflecting the differing aggressiveness of these two models. B, Treatment of KPC‐CAFs (100 000 per Mini‐Organo [2.5 mg/mL Col I]) with the nonmuscle Myosin II inhibitor Blebbistatin shows a dose‐dependent inhibition of the ability of KPC‐CAFs to remodel and contract the Mini‐Organos. C, Treatment of KPC‐CAFs (100 000 per Mini‐Organo [2.5 mg/mL Col I]) with Blebbistatin; the ROCK inhibitor Fasudil or the PHD inhibitor DMOG (which mimics hypoxia) leads to a significant reduction in the contraction of the Mini‐Organos. D‐F, Treatment of (D) human HN‐CAFs (70 000 per Mini‐Organo [3.5 mg/mL Col I + 20% Matrigel]), (E) human V‐CAFs (50 000 per Mini‐Organo [3.5 mg/mL Col I + 20% Matrigel]), and (F) human Cer‐CAFs (50 000 per Mini‐Organo [3.5 mg/mL Col I + 20% Matrigel]) with inhibitors of intracellular force generation (10‐μM Y‐27632, 10‐μM Blebbistatin, 10‐μM Mevastatin, or 10‐μM Verteporfin) show differential effects between the different tumour derived CAFs. G, Treatment of human HN‐CAFS (50 000 per Mini‐Organo [3.5 mg/mL Col I + 20% Matrigel]) and human V‐CAF (40 000 per Mini‐Organo [3.5 mg/mL Col I + 20% Matrigel]) with 2 ng/mL exogenous TGFβ leads to activation and increased contraction. H‐I, Exposure to hypoxia decreases CAF activation leading to a reduced contractile ability, which can be rescued by the addition of exogenous TGFβ in both lines.