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.

Eicosanoids and cancer

“…A statistically significant correlation was also observed in head and neck squamous cell carcinoma. Patients who expressed high levels of PGIS in head and neck squamous cell carcinoma tissues had a higher 5-year survival rate than patients with low levels of PGIS 67 .…”

Differential Expression of Prostaglandin I2 Synthase Associated with Arachidonic Acid Pathway in the Oral Squamous Cell Carcinoma

“…Regarding the head and neck squamous-cell carcinoma type (HNSCC), a study has investigated carbaprostacyclin (cPGI 2 ), a stable analogue of PTGIS, and showed little effect of analogue in cell migration of the HNSCC cell line. Furthermore, the authors suggested that the effect of PTGIS was related to its ability to promote vascularization; also, PTGIS gene and protein expression were shown to be reduced in HNSCC samples compared to non-tumor mucosa [ 63 ].…”

Expression and Cellular Localization of 15-Hydroxy-Prostaglandin-Dehydrogenase in Abdominal Aortic Aneurysm

“…Hypervascularization per se could be a determinant factor in reducing mechanical strength, because it turns the media layer spongy and favors leukocyte-mediated matrix degradation. We have shown that EP-4 activation, which is the main PGE-receptor in endothelial cells, induces angiogenesis [ 16 , 28 ]. Accordingly, MVEC-derived PGE 2 could play key role in the AAA-associated hypervascularization since PGE 2 could be more effective inducing angiogenesis in an autocrine manner.…”