MODULATION OF INTEGRIN-LAMININ RECEPTOR FUNCTION ON MAMMARY-TUMOR CELLS BY PROSTAGLANDIN E(2) RECEPTOR ANTAGONISM

Our previous studies indicate that prostaglandin E(2) (PGE(2)) recepto rs play a role in tumor metastasis [1,2]. We asked if PGE(2) receptor antagonism would affect murine mammary tumor cell attachment to immobi lized laminin, a critical step in metastasis. The PGE(2) receptor anta gonist, LEO101, at a concentration of 20 mu g/ml, inhibited tumor cell attachment to laminin and the laminin-peptide PA-22 by 41 and 82%, re spectively. Immunoprecipitation studies identified the beta 1 integrin subunit as well as the alpha 3 subunit as major membrane components o f these cells, whereas little or no alpha 1, alpha 5 or alpha 6 was de tected. Antibody blocking studies confirmed that these cells use beta 1, but not the alpha 6 subunit, to attach to laminin. Immunoprecipitat ion studies of untreated or LEO101-treated cells indicate that the exp ression of the alpha 3 integrin, but not other integrins, was decrease d by LEO101.