Remodelling the extracellular matrix in development and disease

Box 1 says ECM signals regulate epithelial-cell proliferation and that dysregulated remodelling can exacerbate disease. The section ‘ECM stiffness and remodelling in cancer progression’ says ECM can promote tumour progression and links MMP1 expression to the risk that atypical ductal hyperplasia becomes cancer. It does not establish that deregulated ECM causes or supports epithelial-cell transformation or hyperplasia itself; page numbers were unavailable in our copy. (LLM, conf=0.83)

Box 3 (page unavailable) says ECM stiffening occurs in cancer and contributes to malignant progression. The section “The ECM promotes angiogenesis” (page unavailable) describes ECM effects on tumour blood vessels, but neither passage says that stiffness, rapid proliferation and a poor vessel network cause cellular hypoxia in epithelial-derived tumours. A search for hypoxia found no passage establishing that causal claim. (LLM, conf=0.78)

The Matrix metalloproteinases section calls MMPs the main enzymes of ECM degradation. Box 3 describes MMP9-mediated basement-membrane breakdown at future metastatic sites, and Abnormal release of growth factors during pathogenesis describes MMP9 releasing VEGF during an angiogenic switch. The copy discusses MMP-regulated invasion in mammary-gland development, but does not establish that MMPs are essential for tumour-cell invasion. (LLM, conf=0.87)

Box 1 says ECM components transmit signals regulating adhesion, migration, proliferation, and differentiation, and describes ECM remodelling. It also describes signalling molecules released by the ECM. The passages found do not establish that dynamic changes in ECM components regulate cytoskeletal organization; Box 1 mentions a cytoskeletal connection but not that effect. (LLM, conf=0.86)