Hypoxia and the extracellular matrix: drivers of tumour metastasis

Emerging data indicate that hypoxia and the extracellular matrix (ECM) together might have a crucial role in metastasis. In this Opinion article the authors suggest a model in which multiple microenvironmental signals might converge to synergistically influence metastatic outcome. 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.