Hypoxia and oxidative stress in breast cancer. Hypoxia and tumourigenesis

Abstract

The microenvironmental hypoxia that arises as a consequence of the development of a solid tumour also acts to promote tumour growth. Hypoxia induces the expression of key components of the angiogenic and apoptotic signalling cascades, the glycolytic pathway and various cell-cycle control proteins. At the cellular level it mediates the infiltration and accumulation of tumour-associated macrophages within avascular tumour regions. Complex interactions between tumour cell and macrophage hypoxia-regulated gene products and their associated pathways form the basis for the hypoxic promotion of tumourigenesis and malignant progression.

Figure 1

Hypoxic regulation of pathways promoting tumour growth. The transcriptional level response to hypoxia is amplified by positive feedback mechanisms and substantial crosstalk between the interconnecting pathways, thus providing a strong, co-ordinated response promoting tumourigenesis and malignant progression. EC,endothelial cell; MCP-1, monocyte chemotactic protein 1; PBMC,peripheral blood mononuclear cell; TAM, tumour-associated macrophage; VEGF, vascular endothelial growth factor.