Mechanisms of Vascular Mimicry Impacting Tumor Progression and Response to Therapy in Breast Cancer

Abstract

Vascular mimicry (VM) describes the formation of pseudo blood vessels constructed of tumor cells that have acquired endothelial-like properties. VM channels endow the tumor with an alternative vascular system that directly connects to host blood vessels whose presence is associated with poor prognosis. However, our molecular understanding of how tumor cells acquire endothelial-like characteristics is relatively poor. Here we show that the transcription factor, Foxc2, promotes VM in breast cancer mouse models by driving ectopic expression of endothelial genes in tumor cells, a process which is stimulated by hypoxia. VM-proficient tumors are resistant to anti-angiogenic therapy and suppression of Foxc2 augments response thus motivating the search for VM-inhibitory agents that could form the basis of combination therapies with anti-angiogenics.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2021
Accession Number
AD1176676

Entities

People

  • Gregory Hannon
  • Ian Cannell

Organizations

  • University of Cambridge

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Blood
  • Blood Vessels
  • Breast Cancer
  • Cancer
  • Cardiovascular System
  • Cell Line
  • Cells
  • Combination Therapy
  • Culture Techniques
  • Data Analysis
  • Emerging Technology
  • Gene Expression
  • Governments
  • Low Density
  • Neoplasms
  • Therapy

Fields of Study

  • Biology

Readers

  • Game Theory.
  • Oncology (Cancer Research).