Fig. 4: Matrix elasticity associates with EMT in PDX models of HER2+ breast cancer. | Nature Communications

Fig. 4: Matrix elasticity associates with EMT in PDX models of HER2+ breast cancer.

From: A convolutional neural network STIFMap reveals associations between stromal stiffness and EMT in breast cancer

Fig. 4

a Schematic showing the strategy for implantation of HER2-positive patient-derived xenograft (PDX) breast cancer tissues. Representative images of immunofluorescent staining of active β1 integrin (b), phospho-FAK (c) and YAP (d) in SOFT or STIFF HER2-positive PDX tumors (left). Scale bar, 50 μm. Quantification of average active β1 integrin (b), phospho-FAK (c) and YAP (d) positive cell or nuclear area for all HER2-positive PDX tumors (right). SOFT; n = 6, STIFF; n = 6. e Average number of lung metastases for mice bearing BCM-3963 PDX tumors in SOFT and STIFF ECM stroma as determined by histological analysis. SOFT; n = 10, STIFF; n = 10. f Average size of the metastatic lesions corresponding to the analysis in e. g Analysis as in e for mice bearing BCM-3143B PDX tumors. SOFT; n = 10, STIFF; n = 10. h Analysis as in f for metastatic lesions corresponding to the analysis in g (left). Images of lung metastases for mice bearing BCM-3143B PDX tumors in SOFT and STIFF ECM stroma (right). Scale bar, 100 μm. i Gene ontology (GO) terms from among the top 23 most significantly upregulated, using RNAseq data derived from all HER2-positive PDX tumors generated in SOFT (n = 9) and STIFF (n = 9) ECM stroma (n = 3 for each PDX and condition). j Volcano plot of p-value (-log10) vs. log fold change (logFC) for gene expression from the HALLMARK_epithelial-to-mesenchymal transition gene set for RNAseq data of HER2-positive PDX tumors developed in SOFT and STIFF ECM stroma. k–n qRT-PCR arrays designed to examine EMT related gene expression to analyze RNA isolated from PDX tumors in SOFT and STIFF ECM stroma. SOFT; n = 7, STIFF; n = 7. Bar plots for the average relative expression of the indicated mesenchymal genes. All graphs are presented as mean +/− S.E.M. Statistical tests used were two-sided Mann–Whitney U test (c, f, k–n) and two-sided unpaired t-test (b, d, e, g, h), *P < 0.03, **P < 0.002, ***P < 0.0002, ****P < 0.0001, ns non-significant. Source data are provided as a Source Data file.

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