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. 2022 Oct 3;132(19):e157399. doi: 10.1172/JCI157399

Figure 8. Targeting FAPα+ HSCs disrupts the co-opted sinusoidal blood vessels to overcome bevacizumab treatment resistance.

Figure 8

(A) Therapeutic schedules for bevacizumab (10 mg/kg) and Z-GP-DAVLBH (2 mg/kg) treatment in mice bearing CRCLM xenografts. Tumors were harvested and photographed at the end of experiments. (B) H&E staining of the tumor-liver interface of CRCLM xenografts after Z-GP-DAVLBH treatments. Quantification of RHGP is shown (n = 6). Scale bar: 100 μm. Asterisks indicate tumor necrosis. (C) Immunofluorescence staining of the EpCAM+ tumor cells (green) that infiltrated the liver parenchyma and hijacked the CD31+ sinusoidal blood vessels (red) in the tumor-liver interface of CRCLM xenografts. Scale bar: 20 μm. Quantification of the co-opted sinusoidal blood vessels is shown (n = 6). (D) Immunofluorescence staining of the cleaved-PARP+ (green) apoptotic FAPα+ HSCs (gray) attached to CD31+ sinusoidal blood vessels (red) in the tumor-liver interface of CRCLM xenografts. Scale bar: 10 μm. Yellow arrows indicate the apoptotic cells. Quantification of cleaved-PARP+ HSCs is shown (n = 6). (E) The overall survival curves of mice bearing bevacizumab-resistant CRCLM xenografts treated with vehicle and Z-GP-DAVLBH (n = 6). OS, overall survival; MS, median survival; Bev AR, bevacizumab acquired resistance; Bev IR, bevacizumab intrinsic resistance. Data are presented as mean ± SEM. **P < 0.01; ***P < 0.001 (2-tailed, unpaired t test).