Tumor Microenvironment Influences on Colorectal Cancer Metastasis

The tumour microenvironment (TME) in colorectal cancer (CRC) comprises a dynamic network of non-malignant stromal cells, immune populations, extracellular matrix and soluble factors that collectively determine metastatic potential. Within the primary tumour, cancer-associated fibroblasts remodel the extracellular matrix and secrete growth factors that facilitate epithelial–mesenchymal transition (EMT) and local invasion. Tumour cells co-opt immunosuppressive myeloid populations and regulatory T cells to evade immune surveillance, while neovascularisation supports dissemination. At distant sites such as liver and lung, a premetastatic niche is established by reciprocal signalling between tumour-derived exosomes, resident cells (for example hepatic stellate cells) and recruited bone marrow-derived cells. This niche fosters tumour cell arrest, survival and outgrowth. Dysregulated pathways—including TGF-β signalling, chemokine networks and metabolic reprogramming—underlie these processes. A deeper understanding of TME-mediated crosstalk has informed emerging strategies that target stromal components, reprogramme immune infiltrates and disrupt niche formation, offering new hope for preventing or treating metastatic CRC on a global scale.

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Tumor Microenvironment Influences on Colorectal Cancer Metastasis publication trend

The graph below shows the total number of articles in tumor microenvironment influences on colorectal cancer metastasis across all publications each year (not limited to Nature Index journals).

Technical terms

Tumour microenvironment (TME): The non-cancerous cells, extracellular matrix and soluble factors surrounding tumour cells that influence growth, invasion and therapy response.

Premetastatic niche: A specialised microenvironment in distant organs, established before tumour cell arrival, which supports seeding and survival of disseminated cancer cells.

Cancer-associated fibroblast (CAF): Activated fibroblastic stromal cells that secrete matrix remodellers and growth factors, promoting tumour progression and invasion.

Hepatic stellate cell (HSC): Liver-resident pericyte-like cells that, upon activation, contribute to fibrotic remodelling and can differentiate into CAFs in metastatic niches.

Epithelial–mesenchymal transition (EMT): A cellular programme by which epithelial tumour cells acquire mesenchymal properties, enhancing motility and invasiveness.

References

1. FGF19‐Activated Hepatic Stellate Cells Release ANGPTL4 that Promotes Colorectal Cancer Liver Metastasis. Advanced Science (2024).
2. Liver metastasis from colorectal cancer: pathogenetic development, immune landscape of the tumour microenvironment and therapeutic approaches. Journal of Experimental & Clinical Cancer Research (2023).
3. Colorectal liver metastasis: molecular mechanism and interventional therapy. Signal Transduction and Targeted Therapy (2022).