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Title: GPNMB/OA protein increases the invasiveness of human metastatic prostate cancer cell lines DU145 and PC3 through MMP-2 and MMP-9 activity

Non-metastatic glycoprotein melanoma protein B (GPNMB), also known as osteoactivin (OA) is expressed in a wide array of tumors and represents an emerging target for drug development. In this study, we investigated the role of GPNMB/OA in the progression of human metastatic DU145 and PC3 prostate cancer cells. GPNMB/OA contribution in PCa malignant phenotype has been analyzed by small interfering RNA-induced GPNMB/OA silencing. We found that following GPNMB/OA silencing the migration capability of both DU145 and PC3 cells, evaluated by using in vitro invasivity assay, as well as the metalloproteinases MMP-2 and MMP-9 activity were equally strongly inhibited. By contrast knocking down GPNMB/OA weakly attenuated cell proliferation rate of DU145, an effect that paralleled with an increase number of apoptotic cells. However, PC3 cell growth seems to be not affected by GPNMB/OA. Together, these data reveal that GPNMB/OA acts as a critical molecular mediator promoting the acquisition of the more aggressive, pro-metastatic phenotype distinctive of human DU145 and PC3 cell lines. - Highlights: • GPNMB/OA expression correlates with DU145 and PC3 cells malignant phenotype. • GPNMB/OA silencing affects the migration capability of both DU145 and PC3 cells. • GPNMB/OA increases invasiveness by up-regulating MMPs activity. • GPNMB/OA promotes DU145 andmore » PC3 cells progression into a more aggressive phenotype.« less
Authors:
; ; ; ;  [1] ; ;  [2] ;  [3] ; ; ;  [1] ;  [1]
  1. Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia (Italy)
  2. Division of Urology, Department of Surgery, Radiology and Public Health, University of Brescia, P.le Spedali Civili 1, 25124 Brescia (Italy)
  3. Medical Oncology, Department of Surgery, Radiology, and Public Health, University of Brescia, P.le Spedali Civili 1, 25124 Brescia (Italy)
Publication Date:
OSTI Identifier:
22395885
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 323; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; APOPTOSIS; CELL PROLIFERATION; GLYCOPROTEINS; GROWTH FACTORS; IN VITRO; MELANOMAS; METASTASES; PHENOTYPE; PHOSPHOTRANSFERASES; PLANT TISSUES; POLYMERASE CHAIN REACTION; PROSTATE; RNA