![]() ![]() ![]() Cancer Res 65:9261–9268īos R, Groep P van der, Greijer AE, Shvarts A, Meijer S, Pinedo HM, Semenza GL, Diest PJ van, Wall E van der (2003) Levels of hypoxia-inducible factor-1α independently predict prognosis in patients with lymph node negative breast carcinoma. Proc Natl Acad Sci U S A 102:15593–15598ījorndahl MA, Cao R, Burton JB, Brakenhielm E, Religa P, Galter D, Wu L, Cao Y (2005b) Vascular endothelial growth factor-A promotes peritumoral lymphangiogenesis and lymphatic metastasis. Int J Oncol 20:791–796ījorndahl M, Cao R, Nissen LJ, Clasper S, Johnson LA, Xue Y, Zhou Z, Jackson D, Hansen AJ, Cao Y (2005a) Insulin-like growth factors 1 and 2 induce lymphangiogenesis in vivo. Nat Med 17:1371–1380Īmat S, Penault-Llorca F, Cure H, Le Bouedec G, Achard JL, Van Praagh I, Feillel V, Mouret-Reynier MA, Dauplat J, Chollet P (2002) Scarff-Bloom-Richardson (SBR) grading: a pleiotropic marker of chemosensitivity in invasive ductal breast carcinomas treated by neoadjuvant chemotherapy. ![]() KeywordsĪlitalo K (2011) The lymphatic vasculature in disease. Finally, we discuss the pharmacological inhibition of HIFs as a novel therapeutic approach to block breast cancer metastasis and improve patient survival. We show that HIFs contribute to key aspects of metastatic progression through the transcriptional activation of target genes in BCCs, lymphatic vessels, blood vessels, and supporting stromal cells within the primary tumor. ![]() In this review, we outline emerging HIF-dependent molecular mechanisms that promote the metastatic dissemination of hypoxic BCCs through the lymphatic and circulatory systems. The proliferation of BCCs leads to areas of decreased oxygen availability (intratumoral hypoxia), which drives breast cancer pathogenesis through the activation of hypoxia-inducible factors (HIFs). Mortality in breast cancer patients ultimately results from the dissemination of breast cancer cells (BCCs) from the primary tumor to distant organs (metastasis). ![]()
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