By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- Investigators discuss new findings in Biotechnology. According to news reporting out of Pittsburgh, Pennsylvania, by NewsRx editors, research stated, "The Ptp4a gene family encodes cancer-associated phosphatases with poorly understood in vivo functions. Mice deficient for PTP4A3 exhibit reduced tumor angiogenesis and decreased VEGF-mediated endothelial cell motility and vascular permeability."
Our news journalists obtained a quote from the research from the University of Pittsburgh, "PTP4A3 has an important role in endothelial cell response to proangiogenic VEGF signaling. PTP4A3 appears to be an attractive molecular target for impeding angiogenesis in addition to tumor progression. Protein-tyrosine phosphatase 4A3 (PTP4A3) is highly expressed in multiple human cancers and is hypothesized to have a critical, albeit poorly defined, role in the formation of experimental tumors in mice. PTP4A3 is broadly expressed in many tissues so the cellular basis of its etiological contributions to carcinogenesis may involve both tumor and stromal cells. In particular, PTP4A3 is expressed in the tumor vasculature and has been proposed to be a direct target of vascular endothelial growth factor (VEGF) signaling in endothelial cells. We now provide the first in vivo experimental evidence that PTP4A3 participates in VEGF signaling and contributes to the process of pathological angiogenesis. Colon tumor tissue isolated from Ptp4a3-null mice revealed reduced tumor microvessel density compared with wild type controls. Additionally, vascular cells derived from Ptp4a3-null tissues exhibited decreased invasiveness in an ex vivo wound healing assay. When primary endothelial cells were isolated and cultured in vitro, Ptp4a3-null cells displayed greatly reduced migration compared with wild type cells. Exposure to VEGF led to an increase in Src phosphorylation in wild type endothelial cells, a response that was completely ablated in Ptp4a3-null cells. In loss-of-function studies, reduced VEGF-mediated migration was also observed when human endothelial cells were treated with a small molecule inhibitor of PTP4A3. VEGF-mediated in vivo vascular permeability was significantly attenuated in PTP4A3-deficient mice."
According to the news editors, the research concluded: "These findings strongly support a role for PTP4A3 as an important contributor to endothelial cell function and as a multimodal target for cancer therapy and mitigating VEGF-regulated angiogenesis."
For more information on this research see: Protein-tyrosine Phosphatase 4A3 (PTP4A3) Promotes Vascular Endothelial Growth Factor Signaling and Enables Endothelial Cell Motility. Journal of Biological Chemistry, 2014;289(9):5904-5913. Journal of Biological Chemistry can be contacted at: Amer Soc Biochemistry Molecular Biology Inc, 9650 Rockville Pike, Bethesda, MD 20814-3996, USA. (American Society for Biochemistry and Molecular Biology - www.asbmb.org; Journal of Biological Chemistry - www.jbc.org/)
Our news journalists report that additional information may be obtained by contacting M.W. Zimmerman, University of Pittsburgh, Dept. of Anesthesiol, Pittsburgh, PA 15260, United States. Additional authors for this research include K.E. McQueeney, J.S. Isenberg, B.R. Pitt, K.A. Wasserloos, G.E. Homanics and J.S. Lazo (see also Biotechnology).
Keywords for this news article include: VEGF, Biotechnology, Pittsburgh, Pennsylvania, Angiogenesis, United States, Cell Motility, Protein Kinases, Endothelial Cells, Membrane Proteins, Angiogenic Proteins, Cancer Gene Therapy, Phosphotransferases, Aromatic Amino Acids, Enzymes and Coenzymes, Growth Factor Receptors, North and Central America
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