Osteoactivin (GPNMB) ectodomain protein promotes growth and invasive behavior of human lung cancer cells.
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
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.
Oyewumi Moses O; Manickavasagam Dharani; Novak Kimberly; Wehrung Daniel; Paulic Nikola; Moussa Fouad M; Sondag Gregory R; Safadi Fayez F
Oncotarget
2016
2016-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.18632/oncotarget.7323" target="_blank" rel="noreferrer noopener">10.18632/oncotarget.7323</a>
Screening and identification of novel compounds with potential anti-proliferative effects on gallium-resistant lung cancer through an AXL kinase pathway.
Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology; Antitumor; AXL; Cell Line; Cell Proliferation/drug effects; Cell Survival/drug effects; Dose-Response Relationship; Drug; Drug Resistance; Drug Screening Assays; Gallium; Gallium-resistance; Gallium/pharmacology; Humans; Lung cancer; Lung Neoplasms/drug therapy/*enzymology/*pathology; Molecular Structure; Naphthalenes/chemistry/*pharmacology; Neoplasm/drug effects; Proto-Oncogene Proteins/*antagonists & inhibitors/metabolism; Pyrazoles/chemistry/*pharmacology; Quinolines/chemistry/*pharmacology; Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism; Structure-Activity Relationship; Tetrazoles/chemistry/*pharmacology; Tumor; Virtual screening
The clinical application of gallium compounds as anticancer agents is hampered by development of resistance. As a potential strategy to overcome the limitation, eight series of compounds were identified through virtual screening of AXL kinase homology model. Anti-proliferative studies were carried using gallium-sensitive (S) and gallium-resistant (R) human lung adenocarcinoma (A549) cells. Compounds 5476423 and 7919469 were identified as leads. The IC50 values from treating
Oyewumi Moses O; Alazizi Adnan; Liva Sophia; Lin Li; Geldenhuys Werner J
Bioorganic & medicinal chemistry letters
2014
2014-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.bmcl.2014.07.072" target="_blank" rel="noreferrer noopener">10.1016/j.bmcl.2014.07.072</a>
MicroRNAs and lung cancer: Biology and applications in diagnosis and prognosis.
gene expression; lung cancer; Carcinogenesis; microRNA
MicroRNAs are tiny non-coding RNA molecules which play important roles in the epigenetic control of cellular processes by preventing the translation of proteins from messenger RNAs (mRNAs). A single microRNA can target different mRNAs, and an mRNA can be targeted by multiple microRNAs. Such complex interplays underlie many molecular pathways in cells, and specific roles for many microRNAs in physiological as well as pathological phenomena have been identified. Changes in expression of microRNAs have been associated with a wide variety of disease conditions, and microRNA-based biomarkers are being developed for the identification and monitoring of such states. This review provides a general overview of the current state of knowledge about the biology of microRNAs, and specific information about microRNAs with regard to the diagnosis and prognosis of lung cancer.
Mallick Reema; Patnaik Santosh Kumar; Yendamuri Sai
Journal of carcinogenesis
2010
2010-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.4103/1477-3163.67074" target="_blank" rel="noreferrer noopener">10.4103/1477-3163.67074</a>
Estimating the annual frequency of synchronous brain metastasis in the United States 2010-2013: a population-based study.
Adolescent; Adult; Age Distribution; Aged; Brain Neoplasms/*epidemiology/*secondary; Breast Neoplasms/epidemiology/*pathology; Cancer registries; Community Health Planning; Female; Humans; Lung cancer; Lung Neoplasms/epidemiology/*pathology; Male; Metastatic brain tumors; Middle Aged; Retrospective Studies; SEER; United States/epidemiology; Young Adult
Brain metastases (BM) are one of the most common types of brain tumors and are a relatively common event in the disease process for several high-incidence cancer types, including breast and lung cancers. Historically, information on metastases including BM have not been collected as part of national cancer registration in the US, but BM at time of primary cancer diagnosis (SBM), is now collected by the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) system. Using data from 18 SEER registries from 2010 to 2013, we assessed the frequency of SBM at time of primary diagnosis in the US by site, histology group, sex, race, age, and insurance status. There were 1,634,954 total primary cancer cases in SEER from 2010 to 2013, 1.7% of which presented with SBM. The cancer type with the highest proportion of SBM was lung cancer (10.8% of cases with SBM), followed by esophageal (1.5%), kidney (1.4%), and melanoma (1.2%). SBM varied by age, sex, race, and insurance status for most histologies. Our results reflect the high proportion of patients who are diagnosed with lung cancer at late stages and present with SBM, in contrast to other common cancers in the US where SBM is less common. Demographic variation in molecular subtype and risk behavior may influence variation in SBM. BM is a relatively common event in late stage cancer and cause significant morbidity and mortality, and assessment of accurate population-based data is critical to estimate total disease burden.
Kromer Courtney; Xu Jordan; Ostrom Quinn T; Gittleman Haley; Kruchko Carol; Sawaya Raymond; Barnholtz-Sloan Jill S
Journal of neuro-oncology
2017
2017-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s11060-017-2516-7" target="_blank" rel="noreferrer noopener">10.1007/s11060-017-2516-7</a>