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Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
09:03

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells

Published on: November 23, 2014

Vascular remodeling marks tumors that recur during chronic suppression of angiogenesis

Jianzhong Huang1, Samuel Z Soffer, Eugene S Kim

  • 1Division of Pediatric Surgery, Columbia University College of Physicians and Surgeons, 3959 Broadway, BHN 214, New York, NY 10032, USA.

Molecular Cancer Research : MCR
|February 6, 2004
PubMed

Insights

Tumors can regrow during antiangiogenic therapy by remodeling blood vessels. This enhanced vascular stability, marked by increased mural cell proliferation and specific growth factors, may support recurrent tumor growth.

Area of Science:

  • Oncology
  • Vascular Biology
  • Cancer Therapy

Background:

  • Antiangiogenic therapy theoretically offers an advantage in avoiding acquired resistance due to the normal genetic status of target vasculature.
  • However, tumors can resume growth during prolonged antiangiogenic blockade, with unclear underlying mechanisms.

Purpose of the Study:

  • To investigate the molecular mechanisms of recurrent tumor growth during chronic antiangiogenic therapy.
  • To characterize vascular remodeling in a xenograft model of Wilms' tumor under sustained antiangiogenic blockade.

Main Methods:

  • Utilized a xenograft murine model of human Wilms' tumor.
  • Administered vascular endothelial growth factor blockade, metronomic topotecan chemotherapy, and combination therapy.
  • Analyzed molecular and cellular changes in tumor vasculature during recurrent growth.

Main Results:

  • Tumors resuming growth during antiangiogenic blockade featured remodeled vasculature with increased vessel diameter and mural cell proliferation.
  • Remodeled vessels expressed platelet-derived growth factor-B (PDGF-B) and ephrinB2, indicating enhanced vascular integrity and stromal cell recruitment.
  • These vascular changes suggest a mechanism for increased perfusion supporting recurrent tumor growth.

Conclusions:

  • Chronic antiangiogenesis can induce vascular remodeling characterized by enhanced stability.
  • This vascular adaptation may promote tumor perfusion and facilitate recurrent growth, posing a challenge for sustained therapeutic efficacy.

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