Osteoactivin Promotes Migration of Oral Squamous Cell Carcinomas.
*Cell Movement; Carcinoma; Cell Adhesion; Cell Line; Cell Proliferation; Cell Survival; Enzyme Activation; Gene Expression Regulation; Head and Neck Neoplasms/genetics/*metabolism/pathology; Humans; Integrin beta1/metabolism; Membrane Glycoproteins/genetics/*metabolism; Messenger/metabolism; Mitogen-Activated Protein Kinases/metabolism; Mouth Neoplasms/genetics/*metabolism/pathology; Neoplasm Invasiveness; Neoplastic; Protein Binding; RNA; RNA Interference; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; Squamous Cell/genetics/*metabolism/pathology; Time Factors; Transfection; Tumor
Nearly 50% of patients with oral squamous cell carcinoma (OSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell adhesion, migration, and invasion. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies. The aims were to determine how integrin interactions modulate OA-induced OSCC cell migration; and to investigate OA effects on cell survival and proliferation. We confirmed OA mRNA and protein overexpression in OSCC cell lines. We assessed OA's interactions with integrins using adhesion inhibition assays, fluorescent immunocytochemistry and co-immunoprecipitation. We investigated OA-mediated activation of mitogen-activated protein kinases (MAPKs) and cell survival. Integrin inhibition effects on OA-mediated cell migration were determined. We assessed effects of OA knock-down on cell migration and proliferation. OA is overexpressed in OSCC cell lines, and serves as a migration-promoting adhesion molecule. OA co-localized with integrin subunits, and co-immunoprecipitated with the subunits. Integrin blocking antibodies, especially those directed against the beta1 subunit, inhibited cell adhesion (P = 0.03 for SCC15 cells). Adhesion to OA activated MAPKs in UMSCC14a cells and OA treatment promoted survival of SCC15 cells. Integrin-neutralizing antibodies enhanced cell migration with OA in the extracellular matrix. OA knock-down resulted in decreased proliferation of SCC15 and SCC25 cells, but did not inhibit cell migration. OA in the extracellular matrix promotes OSCC cell adhesion and migration, and may be a novel target in the prevention of HNSCC spread. J. Cell. Physiol. 231: 1761-1770, 2016. (c) 2015 Wiley Periodicals, Inc.
Arosarena Oneida A; Dela Cadena Raul A; Denny Michael F; Bryant Evan; Barr Eric W; Thorpe Ryan; Safadi Fayez F
Journal of cellular physiology
2016
2016-08
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/10.1002/jcp.25279" target="_blank" rel="noreferrer noopener">10.1002/jcp.25279</a>
Inhibition of cartilage degradation and suppression of PGE2 and MMPs expression by pomegranate fruit extract in a model of posttraumatic osteoarthritis.
*Phytotherapy; *Punicaceae; ACLT; Animal; Animals; Anterior Cruciate Ligament/drug effects/metabolism/pathology; Apoptosis; Cartilage/cytology/*drug effects/metabolism/pathology; Chondrocytes/drug effects/metabolism/pathology; Collagen Type II/genetics/metabolism; Dinoprostone/*metabolism; Disease Models; Disease Progression; Female; Fruit; Interleukins/metabolism; Joints/cytology/*drug effects/metabolism/pathology; Male; Messenger/metabolism; Metalloproteases/genetics/*metabolism; Mitogen-Activated Protein Kinases/metabolism; MMPs; NF-kappa B/metabolism; Osteoarthritis; Osteoarthritis/*drug therapy/etiology/metabolism/pathology; PGE(2); Plant Extracts/pharmacology/therapeutic use; Pomegranate; Rabbit; Rabbits; RNA; Synovial Fluid/metabolism
OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degradation in the affected joints. Pomegranate fruit extract (PFE) inhibits cartilage degradation in vitro. The aim of this study was to determine whether oral consumption of PFE inhibits disease progression in rabbits with surgically induced OA. METHODS: OA was surgically induced in the tibiofemoral joints of adult New Zealand White rabbits. In one group, animals were fed PFE in water for 8 wk postsurgery. In the second group, animals were fed PFE for 2 wk before surgery and for 8 wk postsurgery. Histologic assessment and scoring of the cartilage was per Osteoarthritis Research Society International guidelines. Gene expression and matrix metalloproteinases (MMP) activity were determined using quantitative reverse transcriptase polymerase chain reaction and fluorometric assay, respectively. Interleukin (IL)-1 beta, MMP-13, IL-6, prostaglandin (PG)E2, and type II collagen (COL2A1) levels in synovial fluid/plasma/culture media were quantified using enzyme-linked immunosorbent assay. Expression of active caspase-3 and poly (ADP-ribose) polymerase p85 was determined by immunohistochemistry. Effect of PFE and inhibitors of MMP-13, mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB was studied in IL-1 beta-stimulated rabbit articular chondrocytes. RESULTS: Safranin-O-staining and chondrocyte cluster formation was significantly reduced in the anterior cruciate ligament transaction plus PFE fed groups. Expression of MMP-3, MMP-9, and MMP-13 mRNA was higher in the cartilage of rabbits given water alone but was significantly lower in the animals fed PFE. PFE-fed rabbits had lower IL-6,
Akhtar Nahid; Khan Nazir M; Ashruf Omer S; Haqqi Tariq M
Nutrition (Burbank, Los Angeles County, Calif.)
2017
2017-01
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.nut.2016.08.004" target="_blank" rel="noreferrer noopener">10.1016/j.nut.2016.08.004</a>
Phosphatidylinositide 3-kinase regulates angiotensin II-induced cytosolic phospholipase A2 activity and growth in vascular smooth muscle cells.
Angiotensin II/*metabolism; Animals; Arachidonic Acid/metabolism; Arachidonic Acids/pharmacology; Blotting; Cells; Chromones/pharmacology; Cultured; Enzyme Inhibitors/pharmacology; Flavonoids/pharmacology; Group IV Phospholipases A2; Male; Mitogen-Activated Protein Kinases/metabolism; Morpholines/pharmacology; Muscle; Phosphatidylinositol 3-Kinases/*physiology; Phospholipases A/*metabolism; Phospholipases A2; Phosphorylation; Rats; Smooth; Sprague-Dawley; Vascular/drug effects/*growth & development; Western
Angiotensin (Ang) II via the AT(1) receptor acts as a mitogen in vascular smooth muscle cells (VSMC) through stimulation of multiple signaling mechanisms, including tyrosine kinases and mitogen-activated protein kinase (MAPK). In addition, cytosolic phospholipase A(2)(cPLA(2))-dependent release of arachidonic acid (AA) is linked to VSMC growth and we have reported that Ang II stimulates cPLA(2) activity via the AT(1) receptor. The coupling of Ang II to the activation of cPLA(2) appears to involve mechanisms both upstream and downstream of MAPK such that AA stimulates MAPK activity which phosphorylates cPLA(2) to further enhance AA release. However, the upstream mechanisms responsible for activation of cPLA(2) are not well-defined. One possibility includes phosphatidylinositide
Silfani Tonous N; Freeman Ernest J
Archives of biochemistry and biophysics
2002
2002-06
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/S0003-9861(02)00066-8" target="_blank" rel="noreferrer noopener">10.1016/S0003-9861(02)00066-8</a>