Exogenous prostaglandin E2 inhibits TPA induced matrix metalloproteinase-9 production in MCF-7 cells.
Elevated levels of prostaglandin E2 (PGE2) have been reported in many high metastatic human breast cancers, but no relationship between exogenous PGE2 activity, expression of matrix metalloproteinases (MMPs) and metastasis in human tumor cells has been reported. The poorly invasive human breast cancer cell line MCF-7 was cultured for 24h in the presence of both phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, 50 nM) and PGE2 (1 microM) and the activity of MMP-9, one of the MMPs involved in metastasis, was measured, in growth medium by gelatin substrate zymography. TPA induced a strong production of MMP-9 while exogenous PGE2 had no effect on the basal MMP-9 level, but inhibited the TPA induced enzyme expression and matrigel invasiveness. We showed that MCF-7 cells expressed EP2, EP3 and EP4 receptors for PGE2 and that its action was probably mediated by EP4 receptor and adenylyl cyclase activation while cAMP dependent PKA was not involved in the process of inhibition of MMP-9 production. These findings suggest a possible inhibitory role for exogenous PGE2 in the metastatic process development.
Renò
F
F
Human Anatomy Laboratory, Medical Sciences Department, University of Eastern Piedmont A. Avogadro, Via Solaroli 17, 28100 Novara, Italy.
Baj
G
G
Surico
N
N
Cannas
M
M
D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology* / Q000502:physiology; D004338:Drug Combinations; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007797:Laminin; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D061965:Matrix Metalloproteinase Inhibitors; D009362:Neoplasm Metastasis; D011509:Proteoglycans; D011982:Receptors, Prostaglandin / Q000096:biosynthesis; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000096:biosynthesis; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004338:Drug Combinations; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; C545650:PTGER4 protein, human; D011509:Proteoglycans; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; C059485:matrigel; D003094:Collagen; D017868:Cyclic AMP-Dependent Protein Kinases; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate