Prostaglandin E₂ receptor modulation affects tumor cell adhesion to laminin

Abstract

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.

The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin γ1 in human glioblastoma cells

“…The growth of human malignant gliomas may be dependent on certain eicosanoids [12]. The PGE 2 receptor modulates tumor cell adhesion to laminin, which may subsequently affect the in vivo process of metastasis [13]. However, another investigator describes the anticancer effect of COX-2 inhibitors as occurring independent of COX-2 status in glioma cells [4].…”

Issues of Ligand Accessibility and Mobility in Initial Cell Attachment

“…It is believed to interact with an amyloid precursor protein in neural systems 32 and with the prostaglandin E2 receptor in murine mammary adenocarcinoma cells. 33 Studies addressing IKVAVreceptor interactions have shown that the interaction is not divalent cation dependent, as is the case for RGD-integrin receptor binding. 25 Evidence to date points to the fact that the IKVAV receptor is not an integrin-type receptor.…”

“…IKVAV is a peptide sequence derived from the extracellular matrix protein laminin, and has been reported to promote the attachment, spreading, migration, and differentiation of neural cells. ,,− The IKVAV sequence has attracted more and more interest in recent years; however, not much is known about its receptor or any associated signal transduction pathways. It is believed to interact with an amyloid precursor protein in neural systems 32 and with the prostaglandin E2 receptor in murine mammary adenocarcinoma cells . Studies addressing IKVAV-receptor interactions have shown that the interaction is not divalent cation dependent, as is the case for RGD−integrin receptor binding .…”