"Mechanism
of Ang-2 induced endothelial cell retraction"
Gregory Small,
Biology, UMBC,
1000 Hilltop Circle, Baltimore, MD 21250
Brad
Carter, MD, Surgical Oncology,
University of Maryland, Baltimore, Baltimore, MD
HER2, a type I growth
factor receptor, is over expressed in very aggressive MCF-7 metastatic
breast cancer cells. It has been demonstrated that HER2 signaling causes
an upregulation of Angiopoietin-2. Angiopoietin-2, or Ang-2, is a key
protein involved in the process of angiogenesis. The process of angiogenesis
involves endothelial cell dissociation and shape change, followed by the
development of neovessels from existing vessels in the new tumor site.
An invasion of the supporting matrix also occurs. It has been deomstrated
that cells over expressing HER2 cause endothelial cell retraction, and
the production of Ang-2 mRNA is regulated by HER2 signaling.
Our hypothesis is that Angiopoietin-2, a protein over expressed in HER2
cancer cells, is responsible for the retraction of endothelial cells.
Ang-2 is released from the tumor cell and binds to the Tie-2 receptor
which triggers the endothelial cell retraction. The retraction occurs
by inducing the dissociation of the alpha, beta, and gamma catenins from
the VE Cadherin. The dissociation breaks any linkage between the adherens
junction and the cytoskeleton of the cells.
