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, Han W. Tun

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)32156-32171
Number of pages16
JournalOncotarget
Volume7
Issue number22
DOIs
StatePublished - May 31 2016

Keywords

  • CNS lymphoma
  • Invasion
  • NF-κB signaling
  • Osteopontin (OPN)
  • Proliferation

ASJC Scopus subject areas

  • Oncology

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