Protease-activated receptor-2 (PAR-2) in cervical cancer proliferation

• Published in: Gynecologic oncology 2008-01, Vol.108 (1), p.19-26
• Main Authors: Sánchez-Hernández, Pedro Ernesto, Ramirez-Dueñas, Maria Guadalupe, Albarran-Somoza, Benibelks, García-Iglesias, Trinidad, del Toro-Arreola, Alicia, Franco-Topete, Ramón, Daneri-Navarro, Adrian
• Format: Article
• Language: English
• Subjects: Alphapapillomavirus - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Cell Growth Processes - drug effects; Cell Growth Processes - physiology; Cell Line, Tumor; Cervical cancer and cellular proliferation; Female; Flow Cytometry; HeLa Cells; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Neoplasm Staging; Obstetrics and Gynecology; Papillomavirus Infections - metabolism; Papillomavirus Infections - pathology; PAR-2; Paraffin Embedding; Polymerase Chain Reaction; Receptor, PAR-2 - biosynthesis; Trypsin; Trypsin - biosynthesis; Trypsin - pharmacology; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2007.08.083

Abstract Objective. Protease-activated receptor-2 (PAR-2) is a G-protein-coupled receptor that is cleaved and activated by trypsin and tryptase. There is evidence that PAR-2 contributes to tumor progression in stomach, colon, pancreas, prostate and breast cancer patients. However, the role of PAR-2 in cervical cancer is still unknown. The aim of this work was to study the PAR-2 expression in cervical cancer tissues and the effect of PAR-2 activation on cervical cancer proliferation. Methods. Immunohistochemistry was used to analyze PAR-2 expression in fixed paraffin-embedded tumor tissue from 16 patients with invasive cervical cancer. HPV types were identified by PCR. PAR-2 expression in UISO-SQC-1, HeLa, SiHa, CasKi and C-33 A cervical cancer cell lines was evaluated by flow cytometry. Trypsin was detected by Western blot. Tumor proliferation in response to trypsin or agonist peptide was evaluated by the MTT method. Results. A strong correlation between trypsin and PAR-2 expression in five cervical cancer cell lines, in association with proliferative growth in the presence of trypsin or agonist peptide, was found. All tumors from cervical cancer patients expressed PAR-2 (immunoreactive score was higher in poorly differentiated tumors). Conclusions. Results suggest that trypsin and PAR-2 are involved in cervical cancer cell proliferation.