Hypoxia and the extracellular matrix: drivers of tumour metastasis

Daniele M Gilkes; Gregg L Semenza; Denis Wirtz

doi:10.1038/nrc3726

Hypoxia and the extracellular matrix: drivers of tumour metastasis

Nat Rev Cancer. 2014 Jun;14(6):430-9. doi: 10.1038/nrc3726. Epub 2014 May 15.

Authors

Daniele M Gilkes¹, Gregg L Semenza², Denis Wirtz³

Affiliations

¹ 1] Vascular Program, Institute for Cell Engineering, and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. [2] Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
² 1] Vascular Program, Institute for Cell Engineering, and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. [2] Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA. [3] Departments of Pediatrics, Oncology, Medicine, Radiation Oncology and Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
³ 1] Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA. [2] Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA. [3] Departments of Oncology and Pathology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

PMID: 24827502
PMCID: PMC4283800
DOI: 10.1038/nrc3726

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.

Publication types

Review

MeSH terms

Extracellular Matrix / metabolism
Extracellular Matrix / pathology*
Humans
Hypoxia / complications*
Hypoxia / metabolism
Neoplasm Metastasis*
Neoplasms / etiology*
Neoplasms / metabolism
Neoplasms / pathology*

Abstract

Publication types

MeSH terms

Grants and funding