Macrophage infiltration and angiogenesis in human malignancy

Book section : Chapter

It is well recognized that human tumours are hypoxic compared to normal adjacent tissues and that hypoxia is related to a poor outcome regardless of modality of treatment, including surgery alone, radiotherapy or chemotherapy. Hypoxia regulates a complex programme of gene transcription via hypoxia-inducible factors 1 and 2 (HIF-1,-2). We have shown that in breast cancer and many other tumour types, tumour-associated macrophages express high levels of HIF-2α compared to normal tissue macrophages and compared to the tumour. This high macrophage HIF-2α is an independent prognostic factor for poor outcome. The mechanisms up-regulating HIF-2α in macrophages may include inflammatory cytokines as well as hypoxia. Differentiation of monocytes into macrophages increases the basal level of HIF-2α protein and changes the programme of hypoxia. Many of these inducible genes are involved in inflammation and angiogenesis. Thus, the conversion of a peripheral monocyte into a macrophage generates a complex new programme of hypoxia-responsive genes that may contribute to angiogenesis and the complex microenvironment within the tumour, and as such provides important targets for therapy.

Authors: Knowles, H; Leek, R; Harris, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Host title: Cancer and Inflammation
• Pages: 189-269
• Series: Novartis Foundation Symposia
• Series number: 256
• Publication date: 2004-01-23
• DOI: 10.1002/0470856734.ch14
• EISSN: 1935-4657
• ISSN: 1528-2511
• EISBN: 9780470856734
• ISBN: 9780470855102
• Language: English
• Subtype: Chapter