Regulation of macrophage function in tumors: the multifaceted role of NF-κB

The pivotal role of tumor-associated macrophages (TAMs) in tumor progression is now well established. TAMs have been shown to influence multiple steps in tumor development including the growth, survival, invasion, and metastasis of tumor cells as well as angiogenesis and lymphangiogenesis in tumors. The molecular circuits that polarize TAMs toward such a protumoral phenotype are now the focus of intense investigation. The transcription factor, nuclear factor-kappaB (NF-kappaB), is a master regulator of many cellular processes and been shown to regulate various pathways that impact on the function of TAMs. Much evidence for this has come from the use of elegant transgenic murine tumor models in which modification of single components of the NF-kappaB signaling pathway has been shown to regulate the pro-tumor repertoire of TAMs. Here, we outline this evidence and attempt to reconcile the various views that have emerged recently over the exact role of NF-kappaB in this phenomenon.