Extracellular matrix and surrounding tissue microenvironment (ECM/TME)

The extracellular matrix (ECM) and surrounding tissue microenvironment represent a complex, non-cellular network of proteins, glycans, and signaling molecules that provide structural and biochemical support to cells (NCBI, 2002). In healthy tissues, the ECM regulates cell behavior, including proliferation, migration, and differentiation, through physical scaffolding and the sequestration of growth factors (Nature Reviews Molecular Cell Biology, 2014). In pathological states, particularly cancer and fibrosis, the ECM undergoes significant remodeling, becoming dense and stiff, which promotes disease progression and creates a physical barrier to drug delivery (PubMed, 2017). The tumor microenvironment (TME) further includes immune cells, fibroblasts, and blood vessels that interact with the ECM to support tumor growth and immune evasion (Science, 2020). Therapeutic strategies targeting this environment aim to degrade structural components like hyaluronic acid or collagen, inhibit remodeling enzymes like matrix metalloproteinases, or disrupt cell-matrix interactions via integrin signaling (Journal of Hematology & Oncology, 2021). However, the ubiquity of the ECM in normal physiology presents significant challenges for achieving tissue-specific targeting and avoiding systemic toxicity (Nature Reviews Drug Discovery, 2016).

Other names

Extracellular matrixTumor microenvironmentStromaInterstitial matrixBasement membrane

Therapeutic intervention involves the enzymatic degradation of structural components such as hyaluronic acid, the inhibition of matrix-remodeling enzymes like matrix metalloproteinases (MMPs) or lysyl oxidase (LOX), and the blockade of cell-surface receptors like integrins that mediate cell-matrix interactions (PubMed, 2017; Journal of Hematology & Oncology, 2021).