This is a synopsis of the two abstracts that have been submitted to the
Journal of the American Cancer Society. This material is to be treated as
copywritted. Any unauthorized reprinting of this will be prosecuted to the
fullest extent possible!!!!
Abstract
Disintegrins are a class of low molecular weight, RGD-containing,
disulfide rich proteins isolated from snake venom. Disintegrins have been
shown to competitively bind to the integrin heterodimer present on the
cell surface. The disintegrin contortrostatin isolated from the venom of
Agkistrodon contortrix contortrix (southern copperhead) is a potent
inhibitor of adhesion of the human breast cancer cell line MDA-MB-435 and
human Kaposi's sarcoma cell line KSY-1 to immobilized vitronectin and
fibronectin, inhibiting binding by greater than 90%. Furthermore
contortrostatin inhibits MDA-MB-435 and KSY-1 binding to immobilized
vitronectin and fibronectin in a dose dependent manner with an IC50 of 1.5
nM, 18 nM and 1.3 nM, 15 nM respectively. However, contortrostatin has
little effect on the binding of MDA cells to human type I collagen since
this particular cell line has little affinity to this collagen. MDA cells
and KSY-1 cells also bind immobilized contortrostatin and binding is
blocked by GRGDSP and EDTA. Since integrins require metal ions both to
facilitate the noncovalent association of their subunits and for ligand
binding, my results indicate that contortrostatin binds to the integrin
receptors on the surface of the MDA cells and KSY-1 cells through a
RGD-dependent process.
Disclaimer:
Any clinical applications, if any at all due to immunological responses,
are many many years away. These results due however shed further light
onto the metastasis process as well as the role of integrins.
