ABSTRACT
The microenvironment of the tumor plays an important role in facilitating cancer progression and activating dormant cancer cells. Most tumors are infiltrated with inflammatory cells which secrete cytokines such as tumor necrosis factor-alpha (TNF-alpha). To evaluate the role of TNF-alpha in the development of cancer we studied its effects on cell migration with a migration assay. The migrating cell number in TNF-alpha-treated group is about 2-fold of that of the control group. Accordingly, the expression of E-cadherin was decreased and the expression of vimentin was increased upon TNF-alpha treatment. These results showed that TNF-alpha can promote epithelial-mesenchymal transition (EMT) of MCF-7 cells. Further, we found that the expression of Snail, an important transcription factor in EMT, was increased in this process, which is inhibited by the nuclear factor kappa B (NFkB) inhibitor aspirin while not affected by the reactive oxygen species (ROS) scavenger N-acetyl cysteine. Consistently, specific inhibition of NFkB by the mutant IkBalpha also blocked the TNF-alpha-induced upregulation of Snail promoter activity. Thus, the activation of NFkB, which causes an increase in the expression of the transcription factor Snail is essential in the TNF-alpha-induced EMT. ROS caused by TNF-alpha seemed to play a minor role in the TNF-alpha-induced EMT of MCF-7 cells, though ROS per se can promote EMT. These findings suggest that different mechanisms might be responsible for TNF-alpha - and ROS-induced EMT, indicating the need for different strategies for the prevention of tumor metastasis induced by different stimuli.
Subject(s)
Humans , Epithelial Cells/metabolism , Mesoderm/cytology , NF-kappa B/physiology , Reactive Oxygen Species/metabolism , Transcription Factors/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Blotting, Western , Case-Control Studies , Cell Line, Tumor , Cadherins/metabolism , Cell Movement/drug effects , Epithelial Cells/pathology , Mesoderm/metabolism , NF-kappa B/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/physiology , Vimentin/metabolismABSTRACT
Hantaviruses are primarily rodent-borne and transmission is by inhalation of virus-contaminated aerosols of rodent excreta, especially urine and saliva. The genus Hantavirus, family Bunyaviridae, comprises at least 14 serotypes and the symptoms of clinical illness range from mild fever to severe hemorrhagic manifestations with renal complications. Many countries in Southeast Asia are unaware of the importance of hantavirus infections and give them low priority. Malaysia, like other countries in the region, has conducted very few studies on the epidemiology of hantaviruses - and even these were conducted in the 1980s. Using a more extensive range of hantavirus antigens, we conducted a seroprevalence study of rodents and humans and found further evidence of hantavirus infections. Moreover, the data from the antibody profiles strongly suggest the presence of different hantaviruses at the study sites.
Subject(s)
Animals , Antibodies, Viral/blood , Orthohantavirus/immunology , Hantavirus Infections/diagnosis , Humans , Malaysia/epidemiology , Rats , Seroepidemiologic StudiesABSTRACT
Se determinó la presencia de anticuerpos anti-Hantavirus en sueros provenientes de roedores salvajes (de zonas urbanas y de campo) y de laboratorio para estudiar la existencia o no de infección con Hantavirus en la Argentina. Se utilizaron las técnicas de inmunofluorescencia indirecta (IF) y de reducción de placas por neutralización (PRNT). Ciento dos sueros correspondían a roedores de laboratorio pertenecientes a 2 bioterios de Mendoza y a 2 de Buenos Aires; 31 sueros fueron rcogidos de ratas urbanas capturadas en el puerto de Buenos Aires y 30 sueros pertenecían a cricétidos salvajes capturados en campos de Buenos Aires y Mendoza (Tabla 1). Se detectaron anticuerpos anti-Hantavirus en colonias de Rattus norvegicus de 3 de los 4 bioterios estudiados (22,5%) en estos mismos lugares. Previamente se habían detectado anticuerpos en sueros humanos por lo que, descartando otros orígenes para la infección, se determinó que las ratas de laboratorio son los candidatos más probables de diseminación del virus en humanos en estos ambientes. En las ratas del puerto de la ciudad de Buenos Aires no se encontraron anticuerpos ni por IF ni por PRNT. En las colonias de ratones y cricéticos de laboratorio no se encontró infección con Hantavirus, mientras que en cricétidos salvajes se demostró la presencia de Hantavirus tanto en Buenos Aires como en Mendoza. En la naturaleza se encontraron anticuerpos séricos anti-Hantavirus en un cricétido reservorio del virus Junín (agente etiológico de la fiebre...