Cross-Talk between Cancer Cells and the Tumour Microenvironment: The Role of the 5-Lipoxygenase Pathway

Int J Mol Sci. 2017 Jan 24;18(2):236. doi: 10.3390/ijms18020236.

Abstract

5-lipoxygenase is an enzyme responsible for the synthesis of a range of bioactive lipids signalling molecules known collectively as eicosanoids. 5-lipoxygenase metabolites such as 5-hydroxyeicosatetraenoic acid (5-HETE) and a number of leukotrienes are mostly derived from arachidonic acid and have been shown to be lipid mediators of inflammation in different pathological states including cancer. Upregulated 5-lipoxygenase expression and metabolite production is found in a number of cancer types and has been shown to be associated with increased tumorigenesis. 5-lipoxygenase activity is present in a number of diverse cell types of the immune system and connective tissue. In this review, we discuss potential routes through which cancer cells may utilise the 5-lipoxygenase pathway to interact with the tumour microenvironment during the development and progression of a tumour. Furthermore, immune-derived 5-lipoxygenase signalling can drive both pro- and anti-tumour effects depending on the immune cell subtype and an overview of evidence for these opposing effects is presented.

Keywords: 5-lipoxygenase; adipose tissue; angiogenesis; immune cells; leukotrienes; tumour microenvironment.

Publication types

  • Review

MeSH terms

  • Adipose Tissue / immunology
  • Adipose Tissue / metabolism
  • Animals
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Biosynthetic Pathways / drug effects
  • Cell Communication*
  • Cyclooxygenase 2 / metabolism
  • Fibroblasts / immunology
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Immunomodulation
  • Leukotrienes / biosynthesis
  • Lipid Metabolism
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / metabolism
  • Signal Transduction*
  • Tumor Microenvironment* / immunology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Leukotrienes
  • Vascular Endothelial Growth Factor A
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2