Oncotarget

Research Papers:

Osteopontin is a multi-faceted pro-tumorigenic driver for central nervous system lymphoma

Qiu Yushi, Zhimin Li, Christina A. Von Roemeling, Heike Doeppler, Laura A. Marlow, Betty Y.S. Kim, Derek C. Radisky, Peter Storz, John A. Copland and Han W. Tun _

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Oncotarget. 2016; 7:32156-32171. https://doi.org/10.18632/oncotarget.8537

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Abstract

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

Correspondence to:

Han W. Tun, email: tun.han@mayo.edu

Keywords: osteopontin (OPN), CNS lymphoma, proliferation, invasion, NF-κB signaling

Received: February 01, 2016     Accepted: March 04, 2016     Published: April 01, 2016

ABSTRACT

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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