Extracellular Matrix Dynamics in Cancer Microenvironments

The extracellular matrix (ECM) is a complex network of proteins and glycoproteins that provides structural support and biochemical cues to cells. In cancer, the dynamic remodelling of the ECM by both tumour and stromal cells alters tissue stiffness, porosity and molecular composition, thereby shaping a microenvironment that fosters malignancy. Cancer‐associated fibroblasts, immune cells and endothelial cells collaborate to deposit, degrade and cross‐link matrix constituents, generating gradients of mechanical stress and signalling ligands that influence cell proliferation, migration and survival. Mechanical forces transmitted through the ECM activate mechanotransduction pathways, promoting epithelial–mesenchymal transition and enhancing invasive potential. Concurrently, matrix remodelling impedes immune surveillance by creating physical barriers and sequestering growth factors, reducing the efficacy of immunotherapies. The evolving interplay between matrix architecture and cellular behaviour underpins key processes in tumour progression, including angiogenesis, metastatic niche formation and therapy resistance. Understanding the regulatory networks that control ECM dynamics offers avenues to normalise matrix properties, enhance drug delivery and restore anti‐tumour immunity.

Research from Nature Portfolio

Recent studies have characterised how tumour and stromal cells coordinate matrix remodelling to drive progression. One seminal work dissected the bidirectional communication between cancer cells and their microenvironment, demonstrating that tumour‐associated fibroblasts deposit and modify collagen networks to increase matrix stiffness, which in turn activates mechanosensitive signalling pathways in carcinoma cells. This feedback loop accelerates invasion and promotes metastatic colonisation in distant organs.

Another investigation revealed that stromal fibroblasts can facilitate basement membrane breaching in a metalloprotease‐independent manner. By exerting contractile forces, these cells mechanically distort the matrix, creating transient gaps through which cancer cells migrate. This mechanical mode of invasion highlights the importance of targeting cellular contractility alongside proteolytic pathways to impede tumour dissemination.

Extracellular Matrix Dynamics in Cancer Microenvironments publication trend

The graph below shows the total number of articles in extracellular matrix dynamics in cancer microenvironments across all publications each year (not limited to Nature Index journals).

Technical terms

Extracellular matrix (ECM): The non‐cellular scaffold of proteins and carbohydrates surrounding cells in tissues.

Cancer‐associated fibroblasts (CAFs): Stromal cells that remodel the ECM and promote tumour growth and invasion.

Matrix metalloproteinases (MMPs): Enzymes that degrade ECM components to facilitate tissue remodelling and cell migration.

Epithelial–mesenchymal transition (EMT): A process by which epithelial cells acquire mesenchymal traits, enhancing motility and invasiveness.

Mechanotransduction: Cellular signalling triggered by mechanical forces transmitted through the ECM.

References

1. Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments. Molecular Cancer (2023).
2. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nature Communications (2020).
3. Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy. Frontiers in Molecular Biosciences (2020).
4. Cancer-associated fibroblasts induce metalloprotease-independent cancer cell invasion of the basement membrane. Nature Communications (2017).