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Text
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URL Address
<a href="http://doi.org/10.18632/oncotarget.7323" target="_blank" rel="noreferrer noopener">http://doi.org/10.18632/oncotarget.7323</a>
Pages
13932–13944
Issue
12
Volume
7
Dublin Core
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Title
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Osteoactivin (GPNMB) ectodomain protein promotes growth and invasive behavior of human lung cancer cells.
Publisher
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Oncotarget
Date
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2016
2016-03
Subject
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Female; Humans; Animals; Mice; Apoptosis; GPNMB; *Cell Movement; Neoplasm Invasiveness; Membrane Glycoproteins/*metabolism; Biomarkers; *Cell Proliferation; cell adhesion; Cell Adhesion; integrin; lung cancer; Lung Neoplasms/metabolism/*pathology; NSCLC; Protein Domains; Xenograft Model Antitumor Assays; Carcinoma; Cultured; Tumor Cells; Nude; Non-Small-Cell Lung/metabolism/*pathology; Tumor/*metabolism
Creator
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Oyewumi Moses O; Manickavasagam Dharani; Novak Kimberly; Wehrung Daniel; Paulic Nikola; Moussa Fouad M; Sondag Gregory R; Safadi Fayez F
Description
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The potential application of GPNMB/OA as a therapeutic target for lung cancer will require a greater understanding of the impact of GPNMB/OA ectodomain (ECD) protein shedding into tumor tissues. Thus, in this work we characterized GPNMB/OA expression and extent of shedding of its ECD protein while evaluating the impact on lung cancer progression using three non-small cell lung cancer (NSCLC) cell lines: A549, SK-MES-1 and calu-6. We observed a direct correlation (R2 = 0.89) between GPNMB/OA expression on NSCLC cells and the extent of GPNMB/OA ECD protein shedding. Meanwhile, siRNA-mediated knockdown of GPNMB/OA in cancer cells significantly reduced GPNMB/OA ECD protein shedding, migration, invasion and adhesion to extracellular matrix materials. Also, exogenous treatment of cancer cells (expressing low GPNMB/OA) with recombinant GPNMB/OA protein (rOA) significantly facilitated cell invasion and migration, but the effects of rOA was negated by inclusion of a selective RGD peptide. Further studies in athymic (nu/nu) mice-bearing calu-6 showed that intratumoral supplementation with rOA effectively facilitated in vivo tumor growth as characterized by a high number of proliferating cells (Ki67 staining) coupled with a low number of apoptotic cells. Taken together, our results accentuate the relevance of GPNMB/OA ECD protein shedding to progression of lung cancer. Thus, strategies that suppress GPNMB/OA expression on lung cancer cells as well as negate shedding of GPNMB/OA ECD protein are worthy of consideration in lung cancer therapeutics.
Identifier
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<a href="http://doi.org/10.18632/oncotarget.7323" target="_blank" rel="noreferrer noopener">10.18632/oncotarget.7323</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Cell Movement
*Cell Proliferation
2016
Animals
Apoptosis
Biomarkers
Carcinoma
Cell Adhesion
Cultured
Department of Anatomy & Neurobiology
Department of Pharmaceutical Sciences
Female
GPNMB
Humans
integrin
Lung cancer
Lung Neoplasms/metabolism/*pathology
Manickavasagam Dharani
Membrane Glycoproteins/*metabolism
Mice
Moussa Fouad M
NEOMED College of Medicine
NEOMED College of Pharmacy
Neoplasm Invasiveness
Non-Small-Cell Lung/metabolism/*pathology
Novak Kimberly
NSCLC
Nude
Oncotarget
Oyewumi Moses O
Paulic Nikola
Protein Domains
Safadi Fayez F
Sondag Gregory R
Tumor Cells
Tumor/*metabolism
Wehrung Daniel
Xenograft Model Antitumor Assays