GPNMB/OA protein increases the invasiveness of human metastatic prostate cancer cell lines DU145 and PC3 through MMP-2 and MMP-9 activity
- Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia (Italy)
- Division of Urology, Department of Surgery, Radiology and Public Health, University of Brescia, P.le Spedali Civili 1, 25124 Brescia (Italy)
- Medical Oncology, Department of Surgery, Radiology, and Public Health, University of Brescia, P.le Spedali Civili 1, 25124 Brescia (Italy)
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 and PC3 cells progression into a more aggressive phenotype.
- OSTI ID:
- 22395885
- Journal Information:
- Experimental Cell Research, Vol. 323, 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); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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