Oxygenated lipid signaling in tumor-associated macrophages-focus on colon cancer

Abstract

Polyunsaturated fatty acids (PUFAs) are enzymatically converted to a variety of bioactive products through insertion of molecular oxygen. PUFA-derived mediators can have either inflammatory or anti-inflammatory/pro-resolving properties, depending upon their specific structures. The relative harm or benefit of these mediators can also be tissue and context dependent. These mediators play important roles in maintaining homeostasis and their dysregulation is involved in pathogenesis of cancers, especially those associated with chronic inflammation. There is a well-established link between colorectal cancer (CRC) and chronic inflammation. The colon harbors a large population of immune cells, which must be tightly regulated in order to maintain the balance between pathogenic and commensal microbes in the gut. Macrophages are key to the process of distinguishing between potentially harmful antigens/microbes and benign or beneficial signals. Macrophages are often associated with tumors (tumor-associated macrophages (TAMs), including CRC. There is some debate as to the prognostic significance of these TAMs in CRC, with some work suggesting a beneficial impact. The purpose of this review is to give an overview of what is currently known regarding PUFA-derived mediator signaling in tumor-associated macrophages in CRC.

Keywords: Colorectal cancer; Cyclooxygenase; Lipoxygenase; Macrophages; Polyunsaturated fatty acids.