Osteopontin is a multi-faceted pro-tumorigenic driver for central nervous system lymphoma
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Qiu Yushi1,*, Zhimin Li1,*, Christina A. Von Roemeling2,*, Heike Doeppler1, Laura A. Marlow1, Betty Y.S. Kim3, Derek C. Radisky1, Peter Storz1, John A. Copland1, Han W. Tun1,4
1Department of Cancer Biology, Jacksonville, Florida, USA
2Mayo Graduate School, Mayo Clinic, Rochester, Minnesota, USA
3Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida, USA
4Department of Hematology/Oncology, Mayo Clinic, Jacksonville, Florida, USA
*These authors contributed equally to this work
Han W. Tun, email: [email protected]
Keywords: osteopontin (OPN), CNS lymphoma, proliferation, invasion, NF-κB signaling
Received: February 01, 2016 Accepted: March 04, 2016 Published: April 01, 2016
Osteopontin (OPN) is the most upregulated gene in primary central nervous system lymphoma (PCNSL) compared to non-CNS diffuse large B cell lymphoma (DLBCL). We show here that OPN is a key mediator of intracerebral tumor growth, invasion, and dissemination in CNS lymphoma, and that these effects depend upon activation of NF-κB. We further show that activation of NF-κB by OPN occurs through a unique mechanism in which intracellular OPN (iOPN) causes transcriptional downregulation of the NF-κB inhibitors, A20/TNFAIP3 and ABIN1/TNIP1, and secretory OPN (sOPN) promotes receptor-mediated activation of NF-κB. We also identify NF-κB-mediated induction of matrix metalloproteinase-8 (MMP-8) as a specific feature of OPN-mediated tissue invasion. These results implicate OPN as a candidate for development of targeted therapy for patients with PCNSL.
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