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>
Chemopreventive and therapeutic potential of tea polyphenols in hepatocellular cancer.
*Anticarcinogenic Agents; Animal; Animals; Anti-Inflammatory Agents; Antioxidants; Biological Availability; Biological Markers; Carcinoma; Catechin/administration & dosage/analogs & derivatives; Chemoprevention; Disease Models; Hepatocellular – Physiopathology; Hepatocellular – Prevention and Control; Hepatocellular – Therapy; Human; Humans; In Vitro Studies; In Vivo Studies; Liver Neoplasms/*drug therapy/*prevention & control; Mice; Neoplasms – Prevention and Control; Nutrition; Outcomes (Health Care); Phenols – Therapeutic Use; Polyphenols/*administration & dosage/pharmacology; Tea – Therapeutic Use; Tea/*chemistry; Xenograft Model Antitumor Assays
The prophylactic and therapeutic properties of tea have been attributed to green tea catechins and black tea theaflavins besides several other polyphenolic compounds. Tea polyphenols possess potent antioxidant and antiinflammatory properties and modulate several signaling pathways. These biochemical facets of tea polyphenols are responsible for its anticancer properties. Several lethal cancers, such as liver cancer, develop within a background of oxidative stress and inflammation. Liver cancer, also known as hepatocellular carcinoma (HCC), has been shown to occur throughout the world including Asia, Africa, Western Europe, and the United States. Phytochemicals, such as tea polyphenols, provide an effective and promising alternative for the chemoprevention and treatment of HCC. In this article, we systematically review, for the first time, the effects of tea polyphenols in the preclinical in vitro and in vivo HCC models. The review also examines, in critical detail, the biochemical mechanisms involved in the chemopreventive and antineoplastic effects of tea polyphenols in hepatic cancer. Finally, we highlight the role of synergy, bioavailability and pharmacokinetics of tea polyphenols, current status of clinical trials, discuss future directions, and comment on the future challenges involved in the effective use of tea polyphenols for the prevention and management of liver cancer.
Darvesh Altaf S; Bishayee Anupam
Nutrition and cancer
2013
1905-07
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/10.1080/01635581.2013.767367" target="_blank" rel="noreferrer noopener">10.1080/01635581.2013.767367</a>