NF-κB: linking inflammation and immunity to cancer development and progression

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Abstract
Chronic inflammation has been suspected to be an important cause of tumour development. Nuclear factor-κB (NF-κB) activation can contribute to inflammation and tumorigenesis during tumour promotion and progression. In several animal models of inflammation-associated cancer, NF-κB activation prevents the apoptosis of cells that are destined to become tumorigenic by upregulating the expression of anti-apoptotic genes, such as those encoding BCL-XL (B-cell lymphoma XL), BFL1 (a BCL-2-related protein) and GADD45β (growth arrest and DNA-damage-inducible 45β). In myeloid cells, NF-κB activation leads to the transcription of genes encoding growth and survival factors that can promote the proliferation of tumour cells. In a chemically induced model of liver cancer, inhibition of NF-κB activation leads to increased tumour growth, through increased initial death of hepatocytes and increased compensatory proliferation, which is promoted by adjacent Kupffer cells. Serine proteases and other factors that are released by necrotic cells seem to be important stimulators of inflammatory cells, which in turn promote tumour growth. Tumour-necrosis factor and interleukin-6 are important mediators during inflammation and tumour promotion, leading to activation of NF-κB and thereby suppression of cell death and stimulation of cell proliferation. Inhibition of NF-κB during cancer therapy could be a useful strategy, because it would be effective in different cell types. In malignant cells, inhibition would increase susceptibility to apoptosis-inducing agents, and in inflammatory cells, it would inhibit the expression of growth and survival factors.