S1P Provokes Tumor Lymphangiogenesis via Macrophage-Derived Mediators Such as IL-1 β or Lipocalin-2

Mediators Inflamm. 2017;2017:7510496. doi: 10.1155/2017/7510496. Epub 2017 Jul 19.

Abstract

A pleiotropic signaling lipid, sphingosine-1-phosphate (S1P), has been implicated in various pathophysiological processes supporting tumor growth and metastasis. However, there are only a few descriptive studies suggesting a role of S1P in tumor lymphangiogenesis, which is critical for tumor growth and dissemination. Corroborating own data, the literature suggests that apoptotic tumor cell-derived S1P alters the phenotype of tumor-associated macrophages (TAMs) to gain protumor functions. However, mechanistically, the role of TAM-induced lymphangiogenesis has only been poorly described, mostly linked to the production of lymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C) and VEGF-D, or transdifferentiation into lymphatic endothelial cells. Recent findings highlight a rather underappreciated role of S1P in tumor lymphangiogenesis, referring to the production of interleukin-1β (IL-1β) and lipocalin-2 (LCN2) by a tumor-promoting macrophage phenotype. In this review, we aim to provide to the readers with the current understanding of the molecular mechanism how apoptotic cell-derived S1P triggers TAMs to promote lymphangiogenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Interleukin-1beta / metabolism*
  • Lipocalin-2 / genetics
  • Lipocalin-2 / metabolism*
  • Lymphangiogenesis / genetics
  • Lymphangiogenesis / physiology*
  • Lysophospholipids / metabolism*
  • Receptors, Lysosphingolipid / genetics
  • Receptors, Lysosphingolipid / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor C / metabolism

Substances

  • Interleukin-1beta
  • Lipocalin-2
  • Lysophospholipids
  • Receptors, Lysosphingolipid
  • Vascular Endothelial Growth Factor C
  • sphingosine 1-phosphate
  • Sphingosine