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- Title
Hypoxia and TGF-beta drive breast cancer bone metastases through parallel signaling pathways in tumor cells and the bone microenvironment.
- Authors
Dunn, Lauren K; Mohammad, Khalid S; Fournier, Pierrick G J; McKenna, C Ryan; Davis, Holly W; Niewolna, Maria; Peng, Xiang Hong; Chirgwin, John M; Guise, Theresa A
- Abstract
Most patients with advanced breast cancer develop bone metastases, which cause pain, hypercalcemia, fractures, nerve compression and paralysis. Chemotherapy causes further bone loss, and bone-specific treatments are only palliative. Multiple tumor-secreted factors act on the bone microenvironment to drive a feed-forward cycle of tumor growth. Effective treatment requires inhibiting upstream regulators of groups of prometastatic factors. Two central regulators are hypoxia and transforming growth factor (TGF)- beta. We asked whether hypoxia (via HIF-1alpha) and TGF-beta signaling promote bone metastases independently or synergistically, and we tested molecular versus pharmacological inhibition strategies in an animal model.
- Publication
PloS one, 2009, Vol 4, Issue 9, pe6896
- ISSN
1932-6203
- Publication type
Journal Article
- DOI
10.1371/journal.pone.0006896