HER2 Regulation of Angiopoietin-2: A Mechanistic Factor in Metastasis
Abstract
HER2 overexpression is a poor prognostic indicator in breast cancer. HER2 amplification is associated with early tumor dissemination, rapid tumor progression, and increased invasiveness, implying that HER2 has a significant role in the metastatic phenotype. We have demonstrated the two key steps in the metastatic mechanism, angioinvasion and transendothelial migration, are augmented by HER2 expression, and we have linked Angiopoietin-2, a vascular destabilizing protein, to expression of HER2. The objective of this research is to determine if metastatic advantage of HER2 expressing cancer cells is imparted by Angiopoietin-2 production, and further to determine if overexpression of HER2 is linked to Angiopoietin-2 expression. The scope of this research begins with two assays to test angioinvasion and endothelial cell retraction, a key step in transendothelial migration. Using several strategies, the research protocol tests tumor cell production of Angiopoietin-2 or blockade of Angiopoietin-2 to determine if Angiopoietin-2 modulates the metastatic steps in question. Further, breast cancer specimens are tested for concurrent expression of HER2 and Angiopoietin-2, and also correlated with stage and grade of the tumor. In addition, concurrent expression of related receptors (Epidermal Growth Factor receptor, HER3, and HER4) are also tested for correlation of Angiopoietin-2 expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADA398722
Entities
People
- Bradford W. Carter
Organizations
- University of Maryland, Baltimore