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.
Zhang
S Z
SZ
University of Maryland Cancer Center, University of Maryland School of Medicine, Baltimore 21201.
Fulton
A M
AM
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011121:Polyphloretin Phosphate / Q000494:pharmacology*; D017474:Receptors, Laminin / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*
D016023:Integrins; D010455:Peptides; D017474:Receptors, Laminin; D018078:Receptors, Prostaglandin E; D011121:Polyphloretin Phosphate