title: COX2 expression in neuroblastoma increases tumorigenicity but does not affect cell death in response to the COX2 inhibitor celecoxib.
abstract: COX2 is an inducible cyclooxygenase implicated in the metastasis and migration of tumour cells. In neuroblastoma, COX2 expression has been detected in both cell lines and tumours. The treatment of neuroblastoma cells in vitro with celecoxib, a COX2 inhibitor, induces apoptosis. The aim of this study was to investigate the role of COX2 in neuroblastoma tumour biology by creating a cell line in which COX2 could be conditionally expressed. Xenograft studies showed that the conditional expression of COX2 enhanced tumour growth and malignancy. Elevated COX2 expression enhanced the proliferation and migration of neuroblastoma cells in vitro. However, elevated COX2 expression or variation between cell lines did not affect sensitivity to the COX2 inhibitor celecoxib, indicating that celecoxib does not promote cell death through COX2 inhibition. These data show that increased COX2 expression alone can enhance the tumorigenic properties of neuroblastoma cells; however, high levels of COX2 may not be a valid biomarker of sensitivity to non-steroidal anti-inflammatory drugs such as celecoxib.
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Bell
authors.forename: Frida
authors.initials: F
authors.lastname: Ponthan
authors.forename: Claire
authors.initials: C
authors.lastname: Whitworth
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Tweddle
authors.forename: John
authors.initials: J
authors.lastname: Lunec
authors.forename: Christopher P F
authors.initials: CP
authors.lastname: Redfern
mesh_terms: D000818:Animals; D000068579:Celecoxib; D016923:Cell Death; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000201:enzymology* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib