Fig. 2: Regional organisation of ECM is associated with cytoskeletal remodelling, local invasion and metastatic spread in human tumours. | Nature Communications

Fig. 2: Regional organisation of ECM is associated with cytoskeletal remodelling, local invasion and metastatic spread in human tumours.

From: Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis

Fig. 2

a Representative multiplex images of Tumour Body (TB), Proximal Invasive Front (PIF), and Distal Invasive Front (DIF) cores in melanoma patients. Images show merged pan melanoma, pMLC2, and MLC2 markers, with individual stainings. Nuclei are stained blue. QuPath maps display tumor mask, circularity, pMLC2 H-score, and MLC2 H-score. Scale bar: 200 µm. b Quantification of tumour circularity (0–1), Myosin II activity (pMLC2 H-score, 0–300), and MLC2 H-score (0–300). n = 53 patients. c Representative images of melanoma invading cells across PIF and DIF. Scale bar: 30 µm. d Percentage of individual and grouped cells invading PIF and DIF in melanoma. n = 53 patients. e Number of invading melanoma cells/mm² in PIF and DIF. n = 53 patients per group. f Representative images of TB, PIF, and DIF in breast cancer (BRCA). Images show merged CK19, pMLC2, and MLC2 markers, with individual staining. QuPath maps display tumour circularity. Scale bar: 100 µm. g Quantification of tumour circularity, Myosin II activity, and MLC2 H-score in BRCA. n = 30 patients. h Images of BRCA invading cells across PIF and DIF. Scale bar: 20 µm. i Percentage of individual and grouped cells invading PIF and DIF in BRCA. n = 30 patients. j Number of invading BRCA cells/mm² in PIF and DIF. n = 30 patients. k Melanoma invasion by stage (II, III, IV; n = 24 patients) and BRCA invasion by lymph node status (N0, N1; n = 30 patients). l Trichrome staining and fibre extraction in melanoma and BRCA at PIF and DIF. Scale bar: 30 µm. One-way ANOVA with Tukey post-hoc (b, g, k) displayed as truncated violin plots. Two-way ANOVA with Tukey post-hoc (d, i), and Mann-Whitney U test (e, j). Bar graphs (d, i) show mean percentages with standard deviation error bars. Boxplots (e, j) show medians, interquartile ranges, and individual data points. Cartoons in Fig. 2(a, f, l) created in BioRender. Maiques, O. (2025) https://BioRender.com/f02u038https://BioRender.com/n61t687.

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