Hypoxia and the extracellular matrix: drivers of tumour metastasis

DM Gilkes, GL Semenza, D Wirtz - Nature Reviews Cancer, 2014 - nature.com
DM Gilkes, GL Semenza, D Wirtz
Nature Reviews Cancer, 2014nature.com
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 …
Abstract
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.
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