title: Prostacyclin-synthase expression in head and neck carcinoma patients and its prognostic value in the response to radiotherapy.
abstract: Prostacyclin (PGI2 ) plays a role in cancer progression but the mechanism is currently poorly understood. Additionally, no data are available about the prognostic value of the PGI2 pathway in head and neck squamous cell carcinoma (HNSCC) therapy. We evaluated the expression of the PGI2 pathway in HNSCC patients. PGI2 production and PGI synthase (PGIS) expression, in terms of mRNA (RT-PCR) and protein (immunoblotting), were lower in tumour samples than in non-tumoural mucosa, whereas, as expected, COX-2 expression was increased in HNSCC tumour samples. Using local control of the tumour after radiotherapy or chemoradiotherapy as a dependent variable, patients were classified into two categories of PGIS transcript levels. The high-PGIS group had a significantly lower frequency of local and distant failure than the low-PGIS group, and the 5-year cancer-specific survival was higher [90.2% (95% CI 81.0-99.4%) versus 60.5% (95% CI 44.4-76.6%)]. None of the four HNSCC cell lines analysed expressed PGIS and therefore they did not produce PGI2 . However, HNSCC-conditioned media enhanced PGI2 production in endothelial cells (ECs). The stable analogue of PGI2 , carbaprostacyclin (cPGI2 ), exerted little effect on HNSCC cell line migration, and no effect on cell cycle distribution or proliferation rate after radiation injury was observed. Nevertheless, cPGI2 promoted EP-4-dependent in vitro angiogenesis. Von Willebrand factor expression (EC marker) and capillary density were significantly higher in the group of patients with high expression of PGIS. Our results indicate that PGIS expression was associated with radiotherapy efficiency. Although we do not provide direct evidence of a relationship between tumour vascularization and radiotherapy efficiency, our results suggest that the effect of PGI2 is related to its ability to promote vascularization. These results also support the concept that co-adjuvant therapy with PGIS enhancers, such as retinoids, could have therapeutic value for HNSCC treatment.
authors.affiliation: Laboratory of Angiology, Vascular Biology and Inflammation, Institute of Biomedical Research (IIB Sant Pau) and Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Camacho
authors.forename: Zenaida
authors.initials: Z
authors.lastname: Piñeiro
authors.forename: Sonia
authors.initials: S
authors.lastname: Alcolea
authors.forename: Jacinto
authors.initials: J
authors.lastname: García
authors.forename: Josep
authors.initials: J
authors.lastname: Balart
authors.forename: Ximena
authors.initials: X
authors.lastname: Terra
authors.forename: Francesc-Xavier
authors.initials: FX
authors.lastname: Avilés-Jurado
authors.forename: Marta
authors.initials: M
authors.lastname: Soler
authors.forename: Miquel
authors.initials: M
authors.lastname: Quer
authors.forename: Xavier
authors.initials: X
authors.lastname: León
authors.forename: Luis
authors.initials: L
authors.lastname: Vila
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000532:radiotherapy*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D003577:Cytochrome P-450 Enzyme System; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase
keywords: PGI2; endothelial cells; head and neck cancer; prostacyclin synthase; radiotherapy