GPNMB/OA protein increases the invasiveness of human metastatic prostate cancer cell lines DU145 and PC3 through MMP-2 and MMP-9 activity
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.
- University of Brescia Italy
Male, Tissue Inhibitor of Metalloproteinase-2, Membrane Glycoproteins, Tissue Inhibitor of Metalloproteinase-1, Gene Expression, Prostatic Neoplasms, Apoptosis, Apoptosis; GPNMB/osteoactivin; Invasivity; Metalloproteinases; Prostate cancer; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Extracellular Signal-Regulated MAP Kinases; Gene Expression; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Membrane Glycoproteins; Neoplasm Invasiveness; Neoplasm Metastasis; Phosphorylation; Prostatic Neoplasms; RNA Interference; RNA, Messenger; RNA, Small Interfering; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Cell Biology, Matrix Metalloproteinase 9, Cell Movement, Cell Line, Tumor, Humans, Matrix Metalloproteinase 2, Neoplasm Invasiveness, RNA Interference, RNA, Messenger, Neoplasm Metastasis, Phosphorylation, RNA, Small Interfering, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation
Male, Tissue Inhibitor of Metalloproteinase-2, Membrane Glycoproteins, Tissue Inhibitor of Metalloproteinase-1, Gene Expression, Prostatic Neoplasms, Apoptosis, Apoptosis; GPNMB/osteoactivin; Invasivity; Metalloproteinases; Prostate cancer; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Extracellular Signal-Regulated MAP Kinases; Gene Expression; Humans; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Membrane Glycoproteins; Neoplasm Invasiveness; Neoplasm Metastasis; Phosphorylation; Prostatic Neoplasms; RNA Interference; RNA, Messenger; RNA, Small Interfering; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Cell Biology, Matrix Metalloproteinase 9, Cell Movement, Cell Line, Tumor, Humans, Matrix Metalloproteinase 2, Neoplasm Invasiveness, RNA Interference, RNA, Messenger, Neoplasm Metastasis, Phosphorylation, RNA, Small Interfering, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation
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