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Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention


O'Connor, Tracy; Zhou, Xiaolan; Kosla, Jan; et al; Seleznik, Gitta; Bremer, Juliane; Bleul, Sabine; Weber, Achim; Aguzzi, A (2019). Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention. Cancer Cell, 36(3):250-267.e9.

Abstract

How lymphoma cells (LCs) invade the brain during the development of central nervous system lymphoma (CNSL) is unclear. We found that NF-κB-induced gliosis promotes CNSL in immunocompetent mice. Gliosis elevated cell-adhesion molecules, which increased LCs in the brain but was insufficient to induce CNSL. Astrocyte-derived CCL19 was required for gliosis-induced CNSL. Deleting CCL19 in mice or CCR7 from LCs abrogated CNSL development. Two-photon microscopy revealed LCs transiently entering normal brain parenchyma. Astrocytic CCL19 enhanced parenchymal CNS retention of LCs, thereby promoting CNSL formation. Aged, gliotic wild-type mice were more susceptible to forming CNSL than young wild-type mice, and astrocytic CCL19 was observed in both human gliosis and CNSL. Therefore, CCL19-CCR7 interactions may underlie an increased age-related risk for CNSL.

Abstract

How lymphoma cells (LCs) invade the brain during the development of central nervous system lymphoma (CNSL) is unclear. We found that NF-κB-induced gliosis promotes CNSL in immunocompetent mice. Gliosis elevated cell-adhesion molecules, which increased LCs in the brain but was insufficient to induce CNSL. Astrocyte-derived CCL19 was required for gliosis-induced CNSL. Deleting CCL19 in mice or CCR7 from LCs abrogated CNSL development. Two-photon microscopy revealed LCs transiently entering normal brain parenchyma. Astrocytic CCL19 enhanced parenchymal CNS retention of LCs, thereby promoting CNSL formation. Aged, gliotic wild-type mice were more susceptible to forming CNSL than young wild-type mice, and astrocytic CCL19 was observed in both human gliosis and CNSL. Therefore, CCL19-CCR7 interactions may underlie an increased age-related risk for CNSL.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Oncology
Life Sciences > Cell Biology
Life Sciences > Cancer Research
Uncontrolled Keywords:Cell Biology, Cancer Research, Oncology
Language:English
Date:1 September 2019
Deposited On:20 Dec 2019 11:56
Last Modified:29 Jul 2020 12:01
Publisher:Cell Press (Elsevier)
ISSN:1535-6108
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.ccell.2019.08.001
PubMed ID:31526758
Project Information:
  • : FunderSNSF
  • : Grant ID10CO11-111305
  • : Project TitleLes territoires de l'industrie en Europe (1750-2000). Développement, financement et réseaux
  • : FunderFP7
  • : Grant ID120209
  • : Project TitleCSI - Central Nervous System Imaging
  • : FunderFP7
  • : Grant ID201335
  • : Project TitleNANOTEST - Development of methodology for alternative testing strategies for the assessment of the toxicological profile of nanoparticles used in medical diagnostics

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