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, Y S Betty Kim, Derek C Radisky, Peter Storz, John A III Copland, Han W Tun

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

Fingerprint

Osteopontin
Lymphoma
Central Nervous System
Matrix Metalloproteinase 8
Lymphoma, Large B-Cell, Diffuse
Down-Regulation
Growth
Genes

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Osteopontin is a multi-faceted pro-tumorigenic driver for central nervous system lymphoma. / Yushi, Qiu; Li, Zhimin; Von Roemeling, Christina A.; Doeppler, Heike; Marlow, Laura A.; Kim, Y S Betty; Radisky, Derek C; Storz, Peter; Copland, John A III; Tun, Han W.

In: Oncotarget, Vol. 7, No. 22, 31.05.2016, p. 32156-32171.

Research output: Contribution to journalArticle

Yushi, Qiu ; Li, Zhimin ; Von Roemeling, Christina A. ; Doeppler, Heike ; Marlow, Laura A. ; Kim, Y S Betty ; Radisky, Derek C ; Storz, Peter ; Copland, John A III ; Tun, Han W. / Osteopontin is a multi-faceted pro-tumorigenic driver for central nervous system lymphoma. In: Oncotarget. 2016 ; Vol. 7, No. 22. pp. 32156-32171.
@article{eba9d503add94f55b7974b3ebb08bc26,
title = "Osteopontin is a multi-faceted pro-tumorigenic driver for central nervous system lymphoma",
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.",
keywords = "CNS lymphoma, Invasion, NF-κB signaling, Osteopontin (OPN), Proliferation",
author = "Qiu Yushi and Zhimin Li and {Von Roemeling}, {Christina A.} and Heike Doeppler and Marlow, {Laura A.} and Kim, {Y S Betty} and Radisky, {Derek C} and Peter Storz and Copland, {John A III} and Tun, {Han W}",
year = "2016",
month = "5",
day = "31",
doi = "10.18632/oncotarget.8537",
language = "English (US)",
volume = "7",
pages = "32156--32171",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "22",

}

TY - JOUR

T1 - Osteopontin is a multi-faceted pro-tumorigenic driver for central nervous system lymphoma

AU - Yushi, Qiu

AU - Li, Zhimin

AU - Von Roemeling, Christina A.

AU - Doeppler, Heike

AU - Marlow, Laura A.

AU - Kim, Y S Betty

AU - Radisky, Derek C

AU - Storz, Peter

AU - Copland, John A III

AU - Tun, Han W

PY - 2016/5/31

Y1 - 2016/5/31

N2 - 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.

AB - 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.

KW - CNS lymphoma

KW - Invasion

KW - NF-κB signaling

KW - Osteopontin (OPN)

KW - Proliferation

UR - http://www.scopus.com/inward/record.url?scp=84973524645&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973524645&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.8537

DO - 10.18632/oncotarget.8537

M3 - Article

C2 - 27050077

AN - SCOPUS:84973524645

VL - 7

SP - 32156

EP - 32171

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 22

ER -