Matricellular Protein Dynamics in Cancer Progression

Matricellular proteins are a specialised class of extracellular regulators that do not primarily serve structural roles but instead modulate cell–matrix interactions, growth factor signalling and matrix remodelling. In cancer, aberrant expression and processing of matricellular proteins such as SPARC, thrombospondins, periostin, tenascins and the CCN family reshape the tumour microenvironment, driving angiogenesis, immune evasion, invasion and metastasis. Dysregulated matricellular dynamics influence the activation of matrix metalloproteinases, integrin engagement and cytokine presentation, thereby promoting epithelial-mesenchymal transition (EMT), enhanced motility and vascular permeability. Feedback loops between tumour cells, stromal fibroblasts, endothelial cells and immune infiltrates further amplify these effects, creating permissive niches for dissemination. The global significance of this research lies in the identification of matricellular signatures as prognostic biomarkers and in the development of targeted approaches that disrupt pathological matrix signalling, aiming to constrain metastatic spread, restore immune surveillance and improve therapeutic responsiveness.

Research from Nature Portfolio

Recent studies have uncovered a pivotal role for tumour-derived SPARC in the early steps of metastasis. Elevated SPARC secretion by melanoma cells was shown to induce paracellular vascular permeability through endothelial VCAM1 engagement and p38 MAPK activation. Genetic ablation of SPARC in tumour cells or blockade of VCAM1 signalling markedly reduced capillary leakiness and extravasation in lung microvessels, thereby impairing metastatic colonisation. These findings establish a direct functional interaction between a matricellular factor and the endothelial barrier and highlight SPARC–VCAM1 as a targetable axis to prevent cancer cell dissemination.

Matricellular Protein Dynamics in Cancer Progression publication trend

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

Technical terms

Matricellular proteins: Non-structural extracellular proteins that regulate cell–matrix interactions and signalling.

SPARC: Secreted protein acidic and rich in cysteine, a matricellular modulator of collagen deposition, growth factor activity and vascular permeability.

SPOCK1: A secreted proteoglycan that promotes epithelial-mesenchymal transition, matrix metalloproteinase activation and immune modulation in tumours.

Epithelial-mesenchymal transition (EMT): A cellular programme by which epithelial cells acquire migratory mesenchymal traits, facilitating invasion and metastasis.

Extravasation: The process whereby circulating tumour cells traverse the endothelial barrier to colonise distant tissues.

References

1. Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis. Nature Communications (2015).
2. SPOCK1, as a potential prognostic and therapeutic biomarker for lung adenocarcinoma, is associated with epithelial-mesenchymal transition and immune evasion. Journal of Translational Medicine (2023).
3. Proteoglycan SPOCK1 as a Poor Prognostic Marker Promotes Malignant Progression of Clear Cell Renal Cell Carcinoma via Triggering the Snail/Slug-MMP-2 Axis-Mediated Epithelial-to-Mesenchymal Transition. Cells (2023).