Molecular Disruption of Breast Tumor Angiogenesis
Abstract
Continued growth of a malignant tumor beyond a certain critical size is dependent on the development of a network of feeder blood vessels (1,2). Findings from a number of laboratories have indicated that this "angiogenic switch" is higffly-dependent on the temporally-regulated and focalized localization of several extracellular proteases and protease inhibitors involving members of both the plasmin-based and metalloproteinase cascades (3,4). Jn vitro analysis of the requirements for the formation of endothelial tubular networks in various culture model systems implicated both urokinase plasminogen activator (uPA) and its fast-acting type-1 inhibitor (PAI- 1) as necessary to achieve complete angiogenesis, consistent with the "balanced proteolysis" concept of endothelial cell migration (5-7). Recent data in mice genetically-engineered to be deficient in expression of genes that encode specific elements of the plasmin activation system has confirmed the critical importance of PAl-1 synthesis in tumor-induced angiogenesis (5-7). Indeed, the absence of host PAI-1 cpmpletely inhibited local invasion and vascularization of transplanted malignant tumors in PAI-1 null mice (5,6). This inability to mount an angiogenic response, moreover, prevented invasive growth by an aggressive and metastatic tumor type (5,6).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA407423
Entities
People
- Paul J. Higgins
Organizations
- Albany Medical College