The role of IL-6 and STAT3 in inflammation and cancer.
The defense of the host from foreign pathogens is the commonly accepted function of the vertebrate immune system. A complex system consisting of many differing cells and structures communicating by both soluble and cell bound ligands, serves to protect the host from infection, and plays a role in preventing the development of certain types of tumours. Numerous signalling pathways are involved in the coordination of the immune system, serving both to activate and attenuate its responses to attack. The ability of the immune system, specifically those cells involved in acute inflammatory responses, to mediate the directed (and sometimes indirect) killing of cells and pathogens, make it a potential threat to host survival. Furthermore, the production and release of various survival factors such as the pleiotropic cytokine IL-6, a major mediator of inflammation and activator of signal transducer and activator of transcription 3, serves to block apoptosis in cells during the inflammatory process, keeping them alive in very toxic environments. Unfortunately, these same pathways serve also to maintain cells progressing towards neoplastic growth, protecting them from cellular apoptotic deletion and chemotherapeutic drugs. Here, we discuss the relationships between cancer and inflammation, and some of the molecular mechanisms involved in mediating the unintended consequences of host defense and tumour survival.
Hodge
David R
DR
Laboratory of Molecular Immunoregulation, Cytokine Molecular Mechanisms Section, Center for Cancer Research, The National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Hurt
Elaine M
EM
Farrar
William L
WL
D019008:Drug Resistance, Neoplasm / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D050791:STAT Transcription Factors / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D015850:Interleukin-6; D050791:STAT Transcription Factors; D050796:STAT3 Transcription Factor; D011505:Protein-Tyrosine Kinases