Zhiyong Mi, Hongtao Guo, Jovan Markovic and Paul C. Kuo
Osteopontin (OPN) is a secreted phosphoprotein whic h plays a critical role in metastasis of colon, liver , and breast cancers. The canonical pathway for OPN signaling fo cuses on its binding interactions with integrin and CD44 cell surface receptors. However, the binding characteri stics of OPN to integrin and CD44 receptors has not been pre vi- ously examined. In this paper, using MDA-MB231 brea st cancer and SK-Hep-1 liver cancer cells, we determin e the relative binding characteristics of the OPN ligand to its integrin and CD44 cell surface receptors. The appar ent K D ’s for binding to CD44 was 56 μ M and 49 μ M and to integrin was 18 μ M and 17 μ M, in SK-Hep-1 and MDA- MB231, respectively. The CD44/Integrin ratio of OP N bound was 1.3 and 3.8 in SK-Hep-1 and MDA-MB231, respectively. Our results indicate that OPN binds t o it rec- ognized receptors with substantially different affi nities, receptor expression varies between cell types, and signifi- cant OPN cell surface interactions that are integri n- and CD44-independent. These uncharacterized interaction s may reveal important insights into OPN’s role in ca ncer metastasis.
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