Modulation of integrin-laminin receptor function on mammary tumor cells by prostaglandin E2 receptor antagonism

Our previous studies indicate that prostaglandin E2 (PGE2) receptors play a role in tumor metastasis. We asked if PGE2 receptor antagonism would affect murine mammary tumor cell attachment to immobilized laminin, a critical step in metastasis. The PGE2 receptor antagonist, LEO101, at a concentration of 20 micrograms/ml, inhibited tumor cell attachment to laminin and the laminin-peptide PA-22 by 41 and 82%, respectively. Immunoprecipitation studies identified the beta 1 integrin subunit as well as the alpha 3 subunit as major membrane components of these cells, whereas little or no alpha 1, alpha 5 or alpha 6 was detected. Antibody blocking studies confirmed that these cells use beta 1, but not the alpha 6 subunit, to attach to laminin. Immunoprecipitation studies of untreated or LEO101-treated cells indicate that the expression of the alpha 3 integrin, but not other integrins, was decreased by LEO101.