Figure 7.
Inhibition of VWF reduces brain metastasis formation. (A) Quantification of arrested TCs on day 1 after intracardial injection with positive VWF signal. Jimt1, 198 metastases in 3 anti-VWF–treated mice; A2058, 183 metastases in 4 anti-VWF treated mice; H1, 150 metastases in 3 anti-VWF–treated mice. (B) MPLSM in vivo images of Jimt1 breast cancer metastases over time. Asterisks: Unique vessel formations used as reference coordinates. Arrowhead: remaining intravascular VWF accumulation that typically disappeared by day 10. Scale bars: 50 µm. (C) The brain metastatic cascade over 1 month represented as a flowchart to compare isotype control (iso-ctr) vs anti-VWF treatment. For each step of the metastatic cascade, the total number of TCs followed, and the likelihood of these cells to reach the next step (%) is shown. Jimt1, 271 metastases in 3 isotype-ctr mice vs 198 metastases in 3 anti-VWF–treated mice (successful micrometastasis P = .007) vs 169 metastases in 3 delayed anti-VWF–treated mice (successful micrometastasis P = .245). A2058, 161 metastases in 4 isotype-ctr mice vs 106 metastases in 3 anti-VWF–treated mice (successful micrometastasis P = 1.0). H1, 128 metastases in 4 isotype-ctr mice vs 153 metastases in 3 anti-VWF–treated mice (successful micrometastasis P = 1.0). All P values for panel C from χ2 test. (D) Representative H&E-stained brain sections of mice with Jimt1 treated with anti-VWF on days 0 to 28 after TC injection. Number of metastases was counted in whole brain slides (white arrows). The higher magnifications show the morphology of a single brain metastasis and the outline used for area calculations. Vascular co-optive growing metastases presented with extensive perivascular protrusions and showed a diffuse infiltration of TCs into the surrounding parenchyma, which were then counted as parts of 1 major metastasis. Scale bars for the overview: 1 mm; for the zoomed-in view: 200 µm. (E) Quantification of H&E-stained histology slides. Jimt1, 1588 metastases in 3 iso-ctr mice vs 294 metastases in 3 aVWF-treated mice (metastasis area P = .0001; metastasis number P = .0001). A2058, 577 metastases in 3 iso-ctr mice vs 117 metastases in 2 aVWF-treated mice (metastasis area P = c.028; metastasis number P = .0001). All P values for panel D from Student t test. All error bars: 95% CI. *P < .05.

Inhibition of VWF reduces brain metastasis formation. (A) Quantification of arrested TCs on day 1 after intracardial injection with positive VWF signal. Jimt1, 198 metastases in 3 anti-VWF–treated mice; A2058, 183 metastases in 4 anti-VWF treated mice; H1, 150 metastases in 3 anti-VWF–treated mice. (B) MPLSM in vivo images of Jimt1 breast cancer metastases over time. Asterisks: Unique vessel formations used as reference coordinates. Arrowhead: remaining intravascular VWF accumulation that typically disappeared by day 10. Scale bars: 50 µm. (C) The brain metastatic cascade over 1 month represented as a flowchart to compare isotype control (iso-ctr) vs anti-VWF treatment. For each step of the metastatic cascade, the total number of TCs followed, and the likelihood of these cells to reach the next step (%) is shown. Jimt1, 271 metastases in 3 isotype-ctr mice vs 198 metastases in 3 anti-VWF–treated mice (successful micrometastasis P = .007) vs 169 metastases in 3 delayed anti-VWF–treated mice (successful micrometastasis P = .245). A2058, 161 metastases in 4 isotype-ctr mice vs 106 metastases in 3 anti-VWF–treated mice (successful micrometastasis P = 1.0). H1, 128 metastases in 4 isotype-ctr mice vs 153 metastases in 3 anti-VWF–treated mice (successful micrometastasis P = 1.0). All P values for panel C from χ2 test. (D) Representative H&E-stained brain sections of mice with Jimt1 treated with anti-VWF on days 0 to 28 after TC injection. Number of metastases was counted in whole brain slides (white arrows). The higher magnifications show the morphology of a single brain metastasis and the outline used for area calculations. Vascular co-optive growing metastases presented with extensive perivascular protrusions and showed a diffuse infiltration of TCs into the surrounding parenchyma, which were then counted as parts of 1 major metastasis. Scale bars for the overview: 1 mm; for the zoomed-in view: 200 µm. (E) Quantification of H&E-stained histology slides. Jimt1, 1588 metastases in 3 iso-ctr mice vs 294 metastases in 3 aVWF-treated mice (metastasis area P = .0001; metastasis number P = .0001). A2058, 577 metastases in 3 iso-ctr mice vs 117 metastases in 2 aVWF-treated mice (metastasis area P = c.028; metastasis number P = .0001). All P values for panel D from Student t test. All error bars: 95% CI. *P < .05.

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