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Updated: Jul 7, 2026

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
09:04

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors

Published on: March 15, 2016

Sustained VEGF blockade results in microenvironmental sequestration of VEGF by tumors and persistent VEGF receptor-2

Angela Kadenhe-Chiweshe1, Joey Papa, Kimberly W McCrudden

  • 1Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, NY, USA.

Molecular Cancer Research : MCR
|February 1, 2008
PubMed

Insights

Sustained blockade of vascular endothelial growth factor (VEGF) in pediatric cancer led to vessel recovery and tumor growth. Perlecan, an extracellular matrix molecule, sequestered VEGF, promoting vascular survival and treatment resistance.

Area of Science:

  • Oncology
  • Vascular Biology
  • Biochemistry

Background:

  • Vascular endothelial growth factor (VEGF) blockade is a clinical strategy for cancer treatment.
  • Most patients develop progressive disease during anti-VEGF therapy, necessitating an understanding of resistance mechanisms.

Purpose of the Study:

  • To investigate the mechanisms of vascular survival and tumor progression during sustained VEGF blockade in a pediatric cancer model.

Main Methods:

  • Utilized late-stage hepatoblastoma xenografts in a preclinical model.
  • Administered sustained VEGF blockade and analyzed tumor vasculature, VEGF expression, perlecan, heparanase, and endothelial signaling pathways (Akt).

Main Results:

  • Initial tumor regression and vascular collapse were observed, followed by vessel recovery during sustained treatment.
  • Increased tumor expression of perlecan, a heparan sulfate proteoglycan, was noted.
  • VEGF and perlecan accumulated around central vessels, maintaining vascular expression of heparanase and VEGF receptor-2 activation despite circulating VEGF Trap.

Conclusions:

  • A novel mechanism for vascular survival during sustained VEGF blockade involves extracellular matrix molecules like perlecan.
  • Perlecan sequesters and releases biologically active VEGF, contributing to endothelial survival signaling and treatment resistance in pediatric cancer.

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