Popis: |
Integrins area widely distributed family of cell surface alpha/beta heterodimers that bind cells to components of the extracellular matrix and mediate cell-cell interactions. Integrin alpha(v)beta3 interacts with RGD (Arg-Gly-Asp) sequence-containing proteins in the extracellular matrix. The distribution of alpha(v)beta3 is highly restricted, with expression on activated endothelium, activated vascular smooth muscle, tumors, and osteoclasts. Expression of alpha(v)beta3 may contribute to a malignant phenotype by supporting the growth and persistence of small blood vessels that nourish the primary and metastatic tumors and increasing invasive potential. Inhibition of alpha(v)beta3 can modulate tumor-induced angiogenesis and can increase apoptosis of tumor-associated small blood vessels. It might also help control humoral hypercalcemia of malignancy through direct or indirect activity on the osteoclast. Preclinical studies found that several RGD peptidomimetics and a monoclonal antibody to alpha(v)beta3 can inhibit tumor growth by blocking tumor-induced angiogenesis. |