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HER2 signaling--induced microvessel dismantling.

W B Carter1

  • 1Division of Surgical Oncology, University of Maryland, Baltimore, 21201, USA.

Surgery
|August 8, 2001
PubMed
Summary

HER2 signaling in breast cancer promotes metastasis by up-regulating angiopoietin-2 (Ang-2), which disrupts microvessel integrity and may facilitate angioinvasion. This study demonstrates HER2-induced microvessel dismantling, opening pathways for cancer spread.

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HER2/neu over-expression induces endothelial cell retraction.

International journal of cancer·2001

Area of Science:

  • Oncology
  • Cell Biology
  • Vascular Biology

Background:

  • Human epidermal growth factor receptor 2 (HER2) signaling in breast cancer cells confers a metastatic advantage.
  • HER2 signaling up-regulates angiopoietin-2 (Ang-2), disrupting endothelial cell (EC) adherens junctions.
  • HER2 signaling may facilitate angioinvasion by compromising microvessel integrity.

Purpose of the Study:

  • To investigate the role of HER2 signaling in breast cancer-induced microvessel breakdown.
  • To determine if HER2 signaling facilitates angioinvasion by disrupting microvessel integrity.

Main Methods:

  • Rat microvessels were cultured and co-cultured with MCF-7 or HER2-overexpressing MCF-7 (HER) cells.
  • Microvessel integrity was quantified by measuring the cumulative length of intact microvessels.
  • HER2 signaling was modulated using Herceptin or heregulin beta 1; Ang-2 was sequestered using soluble Tie-2/Fc.

Main Results:

  • MCF-7 cells induced a time-dependent loss of microvessel integrity.
  • HER cells caused a 90% reduction in microvessel length within 12 hours (P <.05).
  • Herceptin reduced, while heregulin beta 1 augmented, microvessel dismantling (P <.01); Ang-2 sequestration partially reduced dismantling (P <.01).

Conclusions:

  • HER2 signaling in breast cancer cells induces microvessel dismantling, potentially enabling angioinvasion.
  • Angiopoietin-2 plays a role in this mechanism, but other factors are also involved in microvessel dismantling.

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