The molecular mechanism of CD81 antibody inhibition of metastasis.

Metastases are reduced in CD81KO mice. In addition, a unique anti-CD81 antibody, 5A6, inhibits metastasis in vivo and invasion and migration in vitro. Here, we probed the structural components of CD81 required for the antimetastatic activity induced by 5A6. We found that the removal of either cholesterol or the intracellular domains of CD81 did not affect inhibition by the antibody. We show that the uniqueness of 5A6 is due not to increased affinity but rather to its recognition of a specific epitope on the large extracellular loop of CD81. Finally, we present a number of CD81 membrane-associated partners that may play a role in mediating the 5A6 antimetastatic attributes, including integrins and transferrin receptors.