Fig. 2: Plasminogen activation contributes to ECM remodeling in the leukemic BMM. | Nature Communications

Fig. 2: Plasminogen activation contributes to ECM remodeling in the leukemic BMM.

From: Exploitation of the fibrinolytic system by B-cell acute lymphoblastic leukemia and its therapeutic targeting

Fig. 2

A Immunohistochemistry of fibronectin in bones of WT (black) or ANXA2 KO (gray) recipient mice with BCR-ABL1+ B-ALL (P = 0.04, two-tailed t test, n = 5 mice per group, mean ± SD). B Active plasmin in the medium of primary WT (black) or ANXA2 KO (gray) mesenchymal stromal cells (MSC), macrophages (MΦ) or fibroblasts (P = 0.01, P = 0.0035, P = 0.009, two-way ANOVA, Sidak test, n = 5 biological replicates, mean ± SD), normalized to WT. C Immunofluorescence of fibronectin (green) and 4′,6-diamidino-2-phenylindole (DAPI, blue) with or without activation of plasmin in cultures of WT (black) or ANXA2 KO (gray) MSC (P = 0.0047, two-way ANOVA, Sidak test, n = 6 biological replicates, mean ± SD), normalized to cell number. D Invasion of BCR-ABL1+ BA/F3 cells plated on top of WT (black) or ANXA2 KO MSC (gray) or ANXA2 KO MSC overexpressing (OE) ANXA2 (light gray) (P = 0.0004, P = 0.0005, P = 0.0013, P = 0.001, two-way ANOVA, Tukey test n = 3 biological replicates, mean ± SD), normalized to WT. E Kaplan–Meier-style survival curve of WT (black) versus tPA-knockout (tPA KO; gray) recipient mice with BCR-ABL1+ B-ALL (P = 0.0017, Log-rank test, WT n = 5, tPA KO n = 5). F Number of colonies per plate derived from total bone marrow or spleen cells from WT (black) or tPA KO (gray) recipient mice with BCR-ABL1+ B-ALL (P = 0.023, two-way ANOVA, Tukey test, n = 3 (3 replicates of 3 individual mice per group), mean ± SD). G Immunofluorescence of bones, stained for fibronectin (green) and DAPI (blue), from WT or tPA KO recipient mice with BCR-ABL1+ B-ALL (n = 3 mice per group). H Immunofluorescence of bones, stained for fibronectin (green) and DAPI (blue), from WT or ANXA2 KO recipient mice with BCR-ABL1+ B-ALL. Vehicle or tPA was administered by intrafemoral (i.f.) injection (n = 5 mice per group). I Kaplan–Meier-style survival curve of ANXA2 KO recipient mice with B-ALL treated with vehicle (solid line) or plasmin (dashed line) (P = 0.037, Log-rank test, vehicle n = 10, plasmin n = 12). J Immunofluorescence of bones, stained for fibronectin (green) and DAPI (blue), from ANXA2 KO recipient mice with BCR-ABL1+ B-ALL treated with vehicle or plasmin (n = 4 mice per group). Source data are provided as a Source Data file.

Back to article page