Fig 2: Schematic of the mechanisms underlying TNFSF15 modulation of CD11b+ cell differentiation to vascular pericytes. TNFSF15 stimulates CD11b+ cell production in the bone marrow and facilitates bone marrow-derived CD11b+ cell differentiation into pericytes in cell cultures. Down-regulation of the Wnt3a-VEGFR1 signaling pathway and up-regulation of the CD49e-FN signaling pathway by TNFSF15 are involved. Treatment of tumor-bearing mice with recombinant TNFSF15 enhances the association of bone marrow-derived pericytes with endothelial cells in tumor vessels.

Fig 3: Up-regulation of the CD49e-fibronectin signaling pathway and down-regulation of Wnt3a-VEGFR1 in CD11b+ cells by TNFSF15. (A) Flow cytometry analysis (left) and statistical analysis (right) of the expression of CD49e in myeloid CD11b+ cells with or without TNFSF15 treatment (3 μg/mL) for 3 days. (B) Flow cytometry analysis of the expression of α-SMA in suspended and adherent myeloid CD11b+ cells with or without TNFSF15 treatment (3 μg/mL) for 1 or 3 days. (C) Flow cytometric analysis (left) and statistical analysis (right) of the proportion of VEGFR1 positive cells among myeloid CD11b+ cells with or without TNFSF15 treatment (3 μg/mL) for 3 days. RT-PCR analysis of the mRNA expression of Wnt3a (D) and VEGFR2 (E) in myeloid CD11b+ cells with or without TNFSF15 treatment (3 μg/mL) for 1, 3, 5, or 7 days. Each experiment was conducted 3 times independently, and the results are presented as means ± SD. ns, not significant (P > 0.05); Student’s t test was used to analyze the data (n = 3, **P < 0.01, ***P < 0.001).