Apj+ Vessels Drive Tumor Growth and Represent a Tractable Therapeutic Target

Cell Rep. 2018 Oct 30;25(5):1241-1254.e5. doi: 10.1016/j.celrep.2018.10.015.

Abstract

Identification of cellular surface markers that distinguish tumorous from normal vasculature is important for the development of tumor vessel-targeted therapy. Here, we show that Apj, a G protein-coupled receptor, is highly enriched in tumor endothelial cells but absent from most endothelial cells of adult tissues in homeostasis. By genetic targeting using Apj-CreER and Apj-DTRGFP-Luciferase, we demonstrated that hypoxia-VEGF signaling drives expansion of Apj+ tumor vessels and that targeting of these vessels, genetically and pharmacologically, remarkably inhibits tumor angiogenesis and restricts tumor growth. These in vivo findings implicate Apj+ vessels as a key driver of pathological angiogenesis and identify Apj+ endothelial cells as an important therapeutic target for the anti-angiogenic treatment of tumors.

Keywords: Angiogenesis; Apj; anti-angiogenic treatment; surface marker; tumor therapeutic target; tumorous vessel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Apelin Receptors / metabolism*
  • Blood Vessels / embryology
  • Blood Vessels / metabolism
  • Blood Vessels / pathology*
  • Cell Hypoxia
  • Cell Proliferation
  • Endothelial Cells / metabolism
  • Female
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Molecular Targeted Therapy*
  • Neoplasms / blood supply
  • Neoplasms / pathology*
  • Neovascularization, Pathologic
  • Signal Transduction
  • Tumor Hypoxia
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Apelin Receptors
  • Aplnr protein, mouse
  • Vascular Endothelial Growth Factor A