Hypoxia and the extracellular matrix: drivers of tumour metastasis

By Daniele M. Gilkes, G. Semenza, Denis Wirtz. Nature Reviews. Cancer, 2014

1,385 citations recorded by the source corpus.

Of the deaths attributed to cancer, 90% are due to metastasis, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that hypoxia and the extracellular matrix (ECM) might have crucial roles in metastasis. During tumour evolution, changes in the composition and the overall content of the ECM reflect both its biophysical and biological properties and these strongly influence tumour and stromal cell properties, such as proliferation and motility. Originally thought of as independent contributors to metastatic spread, recent studies have established a direct link between hypoxia and the composition and the organization of the ECM, which suggests a new model in which multiple microenvironmental signals might converge to synergistically influence metastatic outcome.

Subfields: Cancer Research, Oncology, Surgery

View Paper: https://www.semanticscholar.org/paper/111f51a329f8d96c5d55c37ca2dda231e1c9deea

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In Cancer Research

1. P. Calder
2. P. Vaupel
3. A. Mayer

In Oncology

1. Vickie E. Baracos
2. P. Calder
3. P. Vaupel
4. C. Roxburgh

In Surgery

1. P. Calder

Citations in the corpus

• ESPEN expert group recommendations for action against cancer-related malnutrition. (2017, background): “A tumor growing rapidly may outpace its blood supply, resulting in regions of the tumor where the partial pressure of oxygen is significantly lower than in healthy tissues [40].”
• Extracellular matrix (ECM) stiffness and degradation as cancer drivers (2018, background): “ECM stiffness could cause intracellular contractions and a subsequent increase of stiffness in actin cytoskeleton that favors cancer cell migration.(13) In fact, making a contact with collagen bundles within the ECM is for extensive motility of cancer cells.”
• Oxidative Phosphorylation as an Emerging Target in Cancer Therapy (2018, background): “As Gray predicted, and has been frequently subsequently demonstrated, tumor hypoxia results in worse clinical outcomes because hypoxic cells are resistant to cancer therapy, leading to local recurrence and an increased propensity towardmetastasis (38).”
• Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives (2021, background): “In addition, the accumulation of numerous matrix proteins in the ECM also results in a chronic hypoxia state in the TME[[283]].”
• Ferroptosis in cancer: from molecular mechanisms to therapeutic strategies (2024, background): “225 – 227 The hypoxic response is mainly mediated by hypoxia-inducible factors (HIFs) that are widely upregulated in human cancers and play a critical role in enabling cancer cells to adapt to hypoxic environments.”