MMP-9/RECK Imbalance: A Mechanism Associated with High-Grade Cervical Lesions and Genital Infection by Human Papillomavirus and Chlamydia trachomatis

Author(s):Show less -

Discacciati, Michelle G. ^[1] ; Gimenes, Fabrcia ^[2] ; Pennacchi, Paula C. ^[1] ; Faiao-Flores, Fernanda ^[1] ; Zeferino, Luiz C. ^[3] ; Derchain, Sophie M. ^[3] ; Teixeira, Julio C. ^[3] ; Costa, Maria C. ^[4] ; Zonta, Marco ^{[5, 6]} ; Termini, Lara ^[4] ; Boccardo, Enrique ^[7] ; Longatto-Filho, Adhemar ^{[8, 9, 10, 11]} ; Consolaro, Marcia E. L. ^[2] ; Villa, Luisa L. ^{[4, 12]} ; Maria-Engler, Silvya S. ^[1]

Affiliation:Show less -

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Lab Clin Cytopathol, BR-05508900 Sao Paulo - Brazil

^[2] State Univ Maringa UEM, Clin Cytol Lab, Maringa, Parana - Brazil

^[3] State Univ Campinas UNICAMP, Sch Med Sci, Dept Obstet & Gynecol, Campinas, SP - Brazil

^[4] INCT HPV Santa Casa Res Inst, Santa Casa Sao Paulo, Sch Med, Sao Paulo - Brazil

^[5] Univ Fed Sao Paulo, Discipline Infectol, LEMC Lab, Sao Paulo - Brazil

^[6] Univ Santo Amaro, Dept Pathol, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508900 Sao Paulo - Brazil

^[8] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal

^[9] Pio XII Fdn, Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos - Brazil

^[10] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst, Braga - Portugal

^[11] Univ Sao Paulo, Sch Med, Dept Pathol, Lab Med Invest LIM, BR-05508900 Sao Paulo - Brazil

^[12] Univ Sao Paulo, Sch Med, Dept Radiol & Oncol, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION; v. 24, n. 10, p. 1539-1547, OCT 2015.
• Web of Science Citations: 10

Abstract

Background: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis. Methods: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR. Results: We found a higher expression of MMP-9 {[}OR, 4.2; 95% confidence interval (CI), 2.2-7.8] and lower expression of RECK (OR, 0.4; 95% CI, 0.2-0.7) in women with CIN2/CIN3/SCC when compared with women from the control group (no neoplasia/CIN1). A statistically significant association was also found between MMP-9/RECK imbalance and infection by alpha-9 HPV and C. trachomatis. The prevalence of C. trachomatis infection was significantly higher in women with high-grade cervical disease (OR, 3.7; 95% CI, 1.3-11.3). Conclusions: MMP-9/RECK imbalance in cervical smears is significantly associated with high-grade cervical diseases and infection by alpha-9 HPV and C. trachomatis. Impact: MMP-9/RECK imbalance during cervical inflammation induced by C. trachomatis might play a role in HPV-mediated cervical carcinogenesis. (C) 2015 AACR. (AU)

• FAPESP's process: 08/03232-1 - HPV and tumor microenvironment
• Grantee: Luisa Lina Villa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/09746-2 - Relationship between MMP-9 and RECK expression in abnormal cervical smears and clinical evolution of squamous intraepithelial lesion
• Grantee: Michelle Garcia Discacciati de Carvalho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral