What is normal? Apelin and VEGFA , drivers of tumor vessel abnormality

Lena Claesson‐Welsh

doi:10.15252/emmm.201910892

Abstract

In this issue of EMBO Molecular Medicine, Uribesalgo and coworkers show that high Apelin expression correlates with poor survival in advanced breast (MMTV-NeuT) and lung (KRASG12D ) murine tumor models as well as in breast and lung cancer in humans. Combining Apelin inhibition (genetically or using an inactive Apelin agonist) with anti-angiogenic therapy using different small molecular weight kinase inhibitors (sunitinib, axitinib) led to marked delay in breast cancer growth in mice. The vasculature in Apelin-targeted cancer showed normalized features including improved perfusion and reduced leakage. These important data provide a strong incentive to target Apelin in human cancer treatment.

Highlights

In this issue of EMBO Molecular Medicine, Uribesalgo and coworkers show that high Apelin expression correlates with poor survival in advanced breast (MMTV-NeuT) and lung (KRASG12D) murine tumor models as well as in breast and lung cancer in humans
Apelin consists of 13- to 36-residue peptides that bind to the G proteincoupled receptor APJ (Lee et al, 2000)
Apelin belongs to the adipokine family released by adipose tissue, but is expressed by many different cell types

Summary

Introduction

In this issue of EMBO Molecular Medicine, Uribesalgo and coworkers show that high Apelin expression correlates with poor survival in advanced breast (MMTV-NeuT) and lung (KRASG12D) murine tumor models as well as in breast and lung cancer in humans. While Apelin by itself has a minimal effect on angiogenesis during normal development such as the retina vasculature, it causes excessive growth of dilated and tortuous vessels in retinopathies (McKenzie et al, 2012). Cancer is associated with a dysfunctional, morphologically abnormal vasculature characterized by poor vessel stability, obliterated lumen, and excessive leakiness.

Results

Conclusion