Prostaglandin E2 receptor modulation affects tumor cell adhesion to laminin.
We have shown previously that murine mammary adenocarcinoma cells both synthesize prostaglandin E2 (PGE2) and have a high affinity receptor for this ligand. Modulation of either PGE synthesis or PGE receptor function changes the metastatic potential of these cells. Because of the importance of laminin and laminin receptors to the metastatic process, we asked whether or not the PGE receptor participates in tumor cell-laminin interactions. As has been reported for many other tumor cells, laminin and the laminin-derived peptide PA22-2, containing the sequence IKVAV, mediate attachment of line 410.4 mammary tumor cells in vitro. We now demonstrate that the attachment of 410.4 cells to laminin or peptide PA22-2 was significantly inhibited by three PGE receptor antagonists, LE0101, SC19220, and sodium meclofenamate. LE0101 was most active, inhibiting tumor cell adhesion in a dose-dependent manner in the absence of nonspecific toxicity. These receptor antagonists had no effect on the PA22-2-mediated attachment of a PGE receptor negative tumor cell line, except at the highest concentration of LE0101 tested. No inhibition of adhesion to Type I collagen was seen. These results indicate that the PGE2 receptor modulates tumor cell adhesion to laminin which may subsequently affect the in vivo process of metastasis.
University of Maryland Cancer Center, Baltimore.
S Z
SZ
Zhang
A M
AM
Fulton
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D008469:Meclofenamic Acid / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011121:Polyphloretin Phosphate / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000502:physiology*; D018078:Receptors, Prostaglandin E; D014407:Tumor Cells, Cultured
D007797:Laminin; D010455:Peptides; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; C070425:PA22-2; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; D008469:Meclofenamic Acid; D011121:Polyphloretin Phosphate