The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma

Primary CNS lymphoma (PCNSL) is an aggressive brain tumor. Despite improvements in therapeutic algorithms, long-term survival remains rare, illustrating an urgent need for novel therapeutic targets. BAFF-R is a pro-survival receptor expressed on most malignant B cells, including PCNSL. To date, its...

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Main Authors:	Xiaolan Zhou, Matthias Mulazzani, Iven-Alex von Mücke-Heim, Sigrid Langer, Wenlong Zhang, Hellen Ishikawa-Ankerhold, Martin Dreyling, Andreas Straube, Louisa von Baumgarten
Format:	Article
Language:	English
Published:	Frontiers Media S.A. 2020-05-01
Series:	Frontiers in Oncology
Subjects:	PCNSL CRISPR-Cas9 intravital microscopy brain tumor knockout BAFF-R
Online Access:	https://www.frontiersin.org/article/10.3389/fonc.2020.00682/full

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spelling	doaj-1b9584394fa045c8b751992df9db15712020-11-25T03:00:02ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-05-011010.3389/fonc.2020.00682530401The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System LymphomaXiaolan Zhou0Matthias Mulazzani1Iven-Alex von Mücke-Heim2Sigrid Langer3Wenlong Zhang4Hellen Ishikawa-Ankerhold5Martin Dreyling6Andreas Straube7Louisa von Baumgarten8Department of Neurology, Ludwig Maximilians University, Munich, GermanyDepartment of Neurology, Ludwig Maximilians University, Munich, GermanyDepartment of Neurology, Ludwig Maximilians University, Munich, GermanyDepartment of Neurology, Ludwig Maximilians University, Munich, GermanyDepartment of Neurology, Ludwig Maximilians University, Munich, GermanyDepartment of Internal Medicine I, Ludwig Maximilians University, Munich, GermanyDepartment of Internal Medicine III, Ludwig Maximilians University, Munich, GermanyDepartment of Neurology, Ludwig Maximilians University, Munich, GermanyDepartment of Neurology, Ludwig Maximilians University, Munich, GermanyPrimary CNS lymphoma (PCNSL) is an aggressive brain tumor. Despite improvements in therapeutic algorithms, long-term survival remains rare, illustrating an urgent need for novel therapeutic targets. BAFF-R is a pro-survival receptor expressed on most malignant B cells, including PCNSL. To date, its role in PCNSL growth remains elusive. Here, we have created a BAFF-R knockout lymphoma cell line (BAFF-R-KO) using CRISPR-Cas9. In serum-starved conditions, BAFF-R-KO cells exhibit decreased viability in vitro compared to BAFF-R+ cells. Combining an orthotopic mouse model of PCNSL with chronic cranial windows and intravital microscopy, we have demonstrated a significant delay in tumor growth in mice inoculated with BAFF-R-KO cells compared to BAFF-R+ PCNSL. Additionally, median survival of BAFF-R-KO mice was significantly prolonged. Altogether, our results indicate the high potential of BAFF-R as a novel treatment target for PCNSL.https://www.frontiersin.org/article/10.3389/fonc.2020.00682/fullPCNSLCRISPR-Cas9intravital microscopybrain tumorknockoutBAFF-R
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Xiaolan Zhou Matthias Mulazzani Iven-Alex von Mücke-Heim Sigrid Langer Wenlong Zhang Hellen Ishikawa-Ankerhold Martin Dreyling Andreas Straube Louisa von Baumgarten
spellingShingle	Xiaolan Zhou Matthias Mulazzani Iven-Alex von Mücke-Heim Sigrid Langer Wenlong Zhang Hellen Ishikawa-Ankerhold Martin Dreyling Andreas Straube Louisa von Baumgarten The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma Frontiers in Oncology PCNSL CRISPR-Cas9 intravital microscopy brain tumor knockout BAFF-R
author_facet	Xiaolan Zhou Matthias Mulazzani Iven-Alex von Mücke-Heim Sigrid Langer Wenlong Zhang Hellen Ishikawa-Ankerhold Martin Dreyling Andreas Straube Louisa von Baumgarten
author_sort	Xiaolan Zhou
title	The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma
title_short	The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma
title_full	The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma
title_fullStr	The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma
title_full_unstemmed	The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma
title_sort	role of baff-r signaling in the growth of primary central nervous system lymphoma
publisher	Frontiers Media S.A.
series	Frontiers in Oncology
issn	2234-943X
publishDate	2020-05-01
description	Primary CNS lymphoma (PCNSL) is an aggressive brain tumor. Despite improvements in therapeutic algorithms, long-term survival remains rare, illustrating an urgent need for novel therapeutic targets. BAFF-R is a pro-survival receptor expressed on most malignant B cells, including PCNSL. To date, its role in PCNSL growth remains elusive. Here, we have created a BAFF-R knockout lymphoma cell line (BAFF-R-KO) using CRISPR-Cas9. In serum-starved conditions, BAFF-R-KO cells exhibit decreased viability in vitro compared to BAFF-R+ cells. Combining an orthotopic mouse model of PCNSL with chronic cranial windows and intravital microscopy, we have demonstrated a significant delay in tumor growth in mice inoculated with BAFF-R-KO cells compared to BAFF-R+ PCNSL. Additionally, median survival of BAFF-R-KO mice was significantly prolonged. Altogether, our results indicate the high potential of BAFF-R as a novel treatment target for PCNSL.
topic	PCNSL CRISPR-Cas9 intravital microscopy brain tumor knockout BAFF-R
url	https://www.frontiersin.org/article/10.3389/fonc.2020.00682/full
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The Role of BAFF-R Signaling in the Growth of Primary Central Nervous System Lymphoma

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