ABSTRACT
BACKGROUND: Chronic lymphocytic leukemia (CLL) microenvironment plays a critical role in disease pathogenesis. Matrix metalloproteinases (MMPs) are involved in CLL-B cell migration and survival. CD147 is associated with MMPs production by tumor and stromal cells. AIM: To analyze CD147, MMP2 and MMP9 expression in CLL-B cells and its modulation by fibroblasts (Fb)-CLL-B cell interaction. METHODS: CLL-B cells were co-cultured with Fb, as a simulation of CLL microenvironment. CD147 was evaluated in healthy donor (HD)-B cells and CLL-B cells by flow cytometry. MMP2 and MMP9 activity in CLL-plasma samples and conditioned media (CMs) was studied by zymography. RESULTS: MMP9/MMP2 plasma levels were significantly higher in CLL patients than in HD. CD147 expression (median fluorescence intensity) in CLL patients characterized 3 groups: low- (19.1 ± 3.2; n=3), middle- (42.7 ± 12.8; n=18) and high- (76.5 ± 9.6; n=5) related to CD147 expression in HD-B cells. CD147 expression significantly increased in CLL-B cells after Fb-CLL-B cell co-culture. A significant increase in proMMP2 activity was observed in CMs obtained from Fb-CLL-B cell co-cultures in comparison with isolated CLL-B cells. CONCLUSIONS: CD147 expression in CLL-B cells and MMPs secretion was induced by Fb-CLL-B cell contact, suggesting CD147 participation in the CLL pathophysiology.
Subject(s)
B-Lymphocytes/metabolism , Basigin/biosynthesis , Cell Communication , Gene Expression Regulation, Leukemic , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Neoplasm Proteins/biosynthesis , Adult , B-Lymphocytes/pathology , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Stromal Cells/metabolism , Stromal Cells/pathologyABSTRACT
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.
Subject(s)
Low Density Lipoprotein Receptor-Related Protein-1/metabolism , Matrix Metalloproteinase 9/metabolism , Prostate/metabolism , Prostatic Hyperplasia/metabolism , Prostatic Intraepithelial Neoplasia/metabolism , Prostatic Neoplasms/metabolism , Prostatitis/metabolism , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Prostate/pathology , Prostatic Hyperplasia/pathology , Prostatic Intraepithelial Neoplasia/pathology , Prostatic Neoplasms/pathology , Prostatitis/pathologyABSTRACT
The aim of this work was to evaluate by immunohistochemistry (IHC) the expression of both LRP-1 and urokinase-type plasminogen activator receptor (uPAR) at different developmental stages of rat prostate disease by using a prostate cancer model previously developed in our laboratory. We found that LRP-1 was weakly expressed in normal prostates and in rats with hyperplastic glands. The expression of this receptor increased and correlated with the degree of premalignant lesions (PIN I, II, and III). The IHC for uPAR in normal prostates and in premalignant lesions showed a score of immunostaining that correlated with the expression of LRP-1. On the other hand, in prostates with adenocarcinomas and undifferentiated carcinomas, LRP-1 was undetectable or weakly detected, whereas uPAR showed a significantly higher level of expression. Based on the IHC results in rat prostates with premalignant and malignant lesions and considering that LRP-1, by mediating the internalization of uPAR, is involved in the regulation of extracellular matrix remodeling and cell migration, we conclude that a decreased expression of LRP-1 could be involved with the increasing activation of plasminogen activators shown in cancers.