Osteoactivin (GPNMB) ectodomain protein promotes growth and invasive behavior of human lung cancer cells.
Title
Osteoactivin (GPNMB) ectodomain protein promotes growth and invasive behavior of human lung cancer cells.
Creator
Oyewumi Moses O; Manickavasagam Dharani; Novak Kimberly; Wehrung Daniel; Paulic Nikola; Moussa Fouad M; Sondag Gregory R; Safadi Fayez F
Publisher
Oncotarget
Date
2016
2016-03
Description
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.
Subject
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
Identifier
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Citation
Oyewumi Moses O; Manickavasagam Dharani; Novak Kimberly; Wehrung Daniel; Paulic Nikola; Moussa Fouad M; Sondag Gregory R; Safadi Fayez F, “Osteoactivin (GPNMB) ectodomain protein promotes growth and invasive behavior of human lung cancer cells.,” NEOMED Bibliography Database, accessed April 26, 2024, https://neomed.omeka.net/items/show/5035.