Immunosuppression in Cervical Cancer with Special Reference to Arginase Activity

ABSTRACT: Introduction: Cervical cancer is characterized by an immunosuppressive microenvironment and a Th2-type cytokine profile. Expression of arginase (ASE), the enzyme that converts L-arginine into L-ornithine and urea, is stimulated by Th2-type cytokines. Objective: To assess the association of...

Full description

Autores:
Bedoya, Astrid Milena
Tate, David
Baena Zapata, Armando
Córdoba Gómez, Carlos Mario
Borrero Franco, Mauricio
Pareja, René
Rojas, Fredy
Patterson, John
Herrero, Rolando
Zea, Arnold
Sánchez Vásquez, Gloria Inés
Tipo de recurso:
Article of investigation
Fecha de publicación:
2014
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/32451
Acceso en línea:
https://hdl.handle.net/10495/32451
https://www.sciencedirect.com/science/article/pii/S0090825814012190?via%3Dihub
Palabra clave:
Uterine Cervical Neoplasms
Neoplasias del Cuello Uterino
Arginase
Arginasa
Arginine
Arginina
Cytokines
Citocinas
Th1-Th2 Balance
Balance Th1 - Th2
Colombia
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/2.5/co/
Description
Summary:ABSTRACT: Introduction: Cervical cancer is characterized by an immunosuppressive microenvironment and a Th2-type cytokine profile. Expression of arginase (ASE), the enzyme that converts L-arginine into L-ornithine and urea, is stimulated by Th2-type cytokines. Objective: To assess the association of ASE activity and L-Arg metabolism products with cervical cancer. Methods: Sera of 87 and 41 women with histologically confirmed by colposcopy-directed biopsy SCC and CIN3 respectively and 79 with normal cytology or Low-Grade Squamous Intraepithelial Lesion (LSIL), were evaluated. Cytokines were measured using Milliplex Human cytokine/chemokine kit. Arginase (ASE) activity was determined using an enzymatic assay. Levels of L-arginine, L ornithine, putrescine and spermine were determined by HPLC. Results: Significantly higher levels of ASE activity were observed in women with CIN3 (age-adjusted OR: 24.3; 95%CI: 3.82–155) and SCC (AOR: 9.8; 95%CI: 2.34–40.8). As expected, possibly due to high levels of ASE activity, higher levels of L-Arg were negatively associated with CIN3 (AOR: 0.03; 95%CI: 0.004–0.19) and SSC (AOR: 0.06; 95%CI: 0.02–0.24). Consistent with the role of ASE in the conversion of L-arginine to L-ornithine and polyamine production therefrom, women with cervical cancer had higher levels of spermine and putrescine. A correlation analysis revealed a significant albeit weak relationship between high levels of IL-10 and high levels of ASE (Pearson r = 0.32, p-value = 0.003) in women with cervical cancer. Conclusion: This study indicates that ASE activity and L-Arg degradation mechanisms of immunosuppression are present in cervical cancer. The results foster research in the design of possible strategies to inhibit ASE activity for therapy of cervical cancer.