Protease-activated receptor-2 (PAR-2) in cervical cancer proliferation.
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.
Sánchez-Hernández
Pedro Ernesto
PE
Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No 950, Colonia Independencia, Guadalajara, Jalisco, CP 44340, Mexico.
Ramirez-Dueñas
Maria Guadalupe
MG
Albarran-Somoza
Benibelks
B
García-Iglesias
Trinidad
T
del Toro-Arreola
Alicia
A
Franco-Topete
Ramón
R
Daneri-Navarro
Adrian
A
D052685:Alphapapillomavirus / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction; D044464:Receptor, PAR-2 / Q000096:biosynthesis*; D014357:Trypsin / Q000096:biosynthesis / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology
D044464:Receptor, PAR-2; D014357:Trypsin