Abstract
Integrins are heterodimeric molecules that are composed of 18 α-subunits and 8 β-subunits. They exist in 24 distinctive shapes based on combination of these sub-units and are mainly responsible for the adhesion of extracellular matrix (ECM) and immunoglobulin family molecules. Integrins mediate adhesion of epithelial cells to the basement membrane and also help in the migration, proliferation and survival of tumor cells. Studies also reveal that certain integrins act as markers for tumor cells and they also assist in both tumor progression and apoptosis. Studies reveal that unligated integrins in association with caspase 8 result in inhibition of ECM adhesion might result and integrin mediated death (IMD) on the other hand integrins in association with oncogenes or receptor tyrosine kinases can result in enhanced tumorigenesis. Among several types of integrins, αvβ3 and α5β1 have gained importance in anti-angiogenesis studies. Hence the role of antiangiogenesis antagonists has come into light. These include a variety of monoclonal antibodies and peptides. Each one of them has their own mechanism of action and antiangiogenesis activity. Current review aims at studying the phase 1 and 2 trails of these antagonists for anti-angiogenic function.
Highlights
Integrins Integrins are a heterodimeric cell surface receptors that assist in the adhesion of extracellular matrix (ECM) and immunoglobulin family molecules
Integrins inherit kinase functionality by recruiting active kinases such as Focal adhesion kinases (FAK’s) and SRC family kinases (SFK’s), assist in the association of ECM to actin- cytoskeleton by recruiting proteins such as talin, paxilin, α-actinin, tensin and vinculin and further associated with cellular migration and survival the help of PINCH and Parvin
The binding and saturation of integrin α5β1 sites by volociximab was determined as a dose-dependent because estimates of volociximab declined with increasing doses which was achieved at the highest dose of 15 mg/kg. These findings suggested that volociximab can be safely administered to target multistep angiogenesis process in a feasible and safe approach [38]
Summary
Integrins Integrins are a heterodimeric cell surface receptors that assist in the adhesion of extracellular matrix (ECM) and immunoglobulin family molecules. The LM 609 antibody is the most specific anti-integrin αvβ5mAb which blocks the interaction of αvβ5 complex with its matrix ligands and inhibits the cell adhesion [14]. Due to the absence of significant clinical responses, affinity and stability in vivo issues of MEDI-523 encouraged to develop second generation humanized anti integrin αvβ5 monoclonal antibody MEDI-522 (Abegrin).
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