Mónica B Gilardoni1, María M Remedi2, Mabel Oviedo3, Tristán Dellavedova4, Juan P Sarría4, Laura Racca4, Mariana Dominguez4, Claudia G Pellizas2, Ana C Donadio2. 1. Centro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Departamento de Bioquímica Clínica, FCQ-UNC, Córdoba, Argentina. Electronic address: mgilard@fcq.unc.edu.ar. 2. Centro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Departamento de Bioquímica Clínica, FCQ-UNC, Córdoba, Argentina. 3. Histología y Patología, Facultad de Ciencias Médicas, UNC, Córdoba, Argentina. 4. Fundación Urológica Córdoba para la Docencia e Investigación Médica, FUCDIM, Córdoba, Argentina.
Abstract
BACKGROUND: Metalloproteinases (MMPs) are relevant modulators of inflammation, tumor microenvironment, cancer invasion and metastasis. They can be regulated by the Low density lipoprotein Receptor-related Protein 1 (LRP-1), a receptor reported to mediate the clearance of lipoproteins, extracellular matrix (ECM) macromolecules and proteinases. The aim of this study was to evaluate the expression of LRP-1, MMP-2 and MMP-9 across various grades of prostatic diseases as benign prostatic hyperplasia (BPH), BPH plus prostatitis (BPH+P), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PCa). METHODS: LRP-1 was analyzed using immunohistochemistry and MMPs proteolytic activity by zymography in prostate tissues with different prostatic diseases. RESULTS: LRP-1 was detected in epithelial cells in BPH (16/18), BPH+P (21/21) and HGPIN (6/6), with a staining intensity of 1+, 1+/2+ and 3+, respectively. In PCa, LRP-1 was absent in 19/27 samples while a low expression was observed in 8/27 biopsies. MMP-9 activity was higher and statistically significant in PCa than in BPH (p≤0.01). CONCLUSION: Considering that LRP-1, by mediating the clearance of MMPs, is involved in the regulation of ECM remodeling and cell migration, we conclude that a decreased expression of LRP-1 could be involved with the increasing activity of MMPs shown in cancers.
BACKGROUND: Metalloproteinases (MMPs) are relevant modulators of inflammation, tumor microenvironment, cancer invasion and metastasis. They can be regulated by the Low density lipoprotein Receptor-related Protein 1 (LRP-1), a receptor reported to mediate the clearance of lipoproteins, extracellular matrix (ECM) macromolecules and proteinases. The aim of this study was to evaluate the expression of LRP-1, MMP-2 and MMP-9 across various grades of prostatic diseases as benign prostatic hyperplasia (BPH), BPH plus prostatitis (BPH+P), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PCa). METHODS:LRP-1 was analyzed using immunohistochemistry and MMPs proteolytic activity by zymography in prostate tissues with different prostatic diseases. RESULTS:LRP-1 was detected in epithelial cells in BPH (16/18), BPH+P (21/21) and HGPIN (6/6), with a staining intensity of 1+, 1+/2+ and 3+, respectively. In PCa, LRP-1 was absent in 19/27 samples while a low expression was observed in 8/27 biopsies. MMP-9 activity was higher and statistically significant in PCa than in BPH (p≤0.01). CONCLUSION: Considering that LRP-1, by mediating the clearance of MMPs, is involved in the regulation of ECM remodeling and cell migration, we conclude that a decreased expression of LRP-1 could be involved with the increasing activity of MMPs shown in cancers.