title: Implications of Hypoxia in Breast Cancer Metastasis to Bone.
abstract: Most solid tumors contain regions of hypoxia in which increased cell proliferation promotes increased oxygen consumption and the condition is further exacerbated as cancer cells become localized far from a functional blood vessel, further decreasing the oxygen supply. An important mechanism that promotes cell adaptation to hypoxic conditions is the expression of hypoxia-inducible factors (HIFs). Hypoxia-inducible factors transcriptionally regulate many genes involved in the invasion and metastasis of breast cancer cells. Patients, whose primary tumor biopsies show high HIF expression levels, have a greater risk of metastasis. The current review will highlight the potential role of hypoxia in breast cancer metastasis to the bone by considering the regulation of many steps in the metastatic process that include invasion, migration, margination and extravasation, as well as homing signals and regulation of the bone microenvironment.
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA. dgilkes1@jhu.edu.|Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA. dgilkes1@jhu.edu.
authors.forename: Daniele M
authors.initials: DM
authors.lastname: Gilkes
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D000860:Hypoxia; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D020782:Matrix Metalloproteinases
keywords: bone; breast cancer; hypoxia; hypoxia-inducible factors (HIFs); invasion; metastasis; migration