The hypoxic tumor microenvironment: A driving force for breast cancer progression

Biochim Biophys Acta. 2016 Mar;1863(3):382-391. doi: 10.1016/j.bbamcr.2015.05.036. Epub 2015 Jun 14.


Intratumoral hypoxia is a common finding in breast cancer and is associated with a significantly increased risk of metastasis and patient mortality. Hypoxia-inducible factors activate the transcription of a large battery of genes encoding proteins that promote primary tumor vascularization and growth, stromal cell recruitment, extracellular matrix remodeling, premetastatic niche formation, cell motility, local tissue invasion, extravasation at sites of metastasis, and maintenance of the cancer stem cell phenotype that is required to generate secondary tumors. Recent preclinical studies suggest that the combination of cytotoxic chemotherapy with drugs that inhibit hypoxia-inducible factors may improve outcome for women with triple-negative breast cancer. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

Keywords: Bone metastasis; Lung metastasis; Lymph node metastasis; Mesenchymal stem cells; Microvesicles; Myeloid-derived suppressor cells; Tumor-associated macrophages.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Cell Hypoxia*
  • Cell Movement*
  • Disease Progression
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1 / metabolism
  • Models, Biological*
  • Tumor Microenvironment*


  • Hypoxia-Inducible Factor 1