Hypoxia and the extracellular matrix: drivers of tumour metastasis.
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.
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.
Daniele M
DM
Gilkes
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.
Gregg L
GL
Semenza
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.
Denis
D
Wirtz
D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*