Fig. 3: Transcriptomic and functional analysis of ECM remodeling in VEGFR2^WT and VEGFR2^R1032Q Sk-Mel-31-derived tumors.

A Pie chart of differentially expressed genes in VEGFR2^R1032Q Sk-Mel-31-derived tumors vs VEGFR2^WT, upregulated (red) and downregulated (blue) genes (n = 4). B Gene ontology (GO) enrichment analysis of differentially expressed genes. Bubble size represents the number of genes associated with each term, and color indicates significance. C Hierarchical clustering of enriched biological processes. D mRNA expression levels of ECM components. Data are presented as fold change relative to VEGFR2^WT Sk-Mel-31-derived tumors. Data comes from n = 2 independent experiment and from n = 4–5 replicates. E Volcano plot of differentially expressed ECM-modifying enzymes. Dashed lines indicate significance thresholds. F Log2 relative expression of MMPs and ADAMTS proteases in VEGFR2^WT -and VEGFR2^R1032Q Sk-Mel-31-derived tumors. Data comes from n = 2 independent experiment and from n = 3 replicates. G In vivo imaging of proteolytic activity using MMPSense probes in tumor-bearing mice. H Quantification of fluorescence signal intensity. Single data are represented as empty dots in Min to Max box & whiskers plot (n = 6–8). Statistical significance was determined by two-way ANOVA, **P < 0.01. I Ex vivo imaging of proteolytic activity using DQ-gelatin probe. Scale bar, 50 µm. J Quantification of DQ-gelatin degradation area. Single data are represented as empty dots in Min to Max box & whiskers plot (n = 4–5). Statistical significance was determined by two-way ANOVA, ***P < 0.001.