Role of VEGFs/VEGFR-1 signaling and its inhibition in modulating tumor invasion: Experimental evidence in different metastatic cancer models

Claudia Ceci, Maria Grazia Atzori, Pedro Miguel Lacal, Grazia Graziani

Research output: Contribution to journalReview articlepeer-review

Abstract

The vascular endothelial growth factor (VEGF) family members, VEGF-A, placenta growth factor (PlGF), and to a lesser extent VEGF-B, play an essential role in tumor-associated angiogenesis, tissue infiltration, and metastasis formation. Although VEGF-A can activate both VEGFR-1 and VEGFR-2 membrane receptors, PlGF and VEGF-B exclusively interact with VEGFR- 1. Differently from VEGFR-2, which is involved both in physiological and pathological angiogenesis, in the adult VEGFR-1 is required only for pathological angiogenesis. Besides this role in tumor endothelium, ligand-mediated stimulation of VEGFR-1 expressed in tumor cells may directly induce cell chemotaxis and extracellular matrix invasion. Furthermore, VEGFR-1 activation in myeloid progenitors and tumor-associated macrophages favors cancer immune escape through the release of immunosuppressive cytokines. These properties have prompted a number of preclinical and clinical studies to analyze VEGFR-1 involvement in the metastatic process. The aim of the present review is to highlight the contribution of VEGFs/VEGFR-1 signaling in the progression of different tumor types and to provide an overview of the therapeutic approaches targeting VEGFR-1 currently under investigation.

Original languageEnglish
Article number1388
JournalInternational Journal of Molecular Sciences
Volume21
Issue number4
DOIs
Publication statusPublished - Feb 2 2020

Keywords

  • Angiogenesis
  • Cancer
  • Flt-1
  • Immune escape
  • Melanoma
  • Metastasis
  • PlGF
  • VEGF-A
  • VEGFR-1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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