title: GPNMB/OA protein increases the invasiveness of human metastatic prostate cancer cell lines DU145 and PC3 through MMP-2 and MMP-9 activity.
abstract: 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.
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fiorentini
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Bodei
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bedussi
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Fragni
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia, Italy.
authors.forename: Sara Anna
authors.initials: SA
authors.lastname: Bonini
authors.affiliation: Division of Urology, Department of Surgery, Radiology and Public Health, University of Brescia, P.le Spedali Civili 1, 25124 Brescia, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Simeone
authors.affiliation: Division of Urology, Department of Surgery, Radiology and Public Health, University of Brescia, P.le Spedali Civili 1, 25124 Brescia, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Zani
authors.affiliation: Medical Oncology, Department of Surgery, Radiology, and Public Health, University of Brescia, P.le Spedali Civili 1, 25124 Brescia, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Missale
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Memo
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia, Italy.
authors.forename: PierFranco
authors.initials: P
authors.lastname: Spano
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia, Italy. Electronic address: sigala@med.unibs.it.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sigala
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000473:pathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
chemical_list: C503042:GPNMB protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D048049:Extracellular Signal-Regulated MAP Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Apoptosis; GPNMB/osteoactivin; Invasivity; Metalloproteinases; Prostate cancer