Oncotarget

Research Papers:

ACKR3 expression on diffuse large B cell lymphoma is required for tumor spreading and tissue infiltration

Viola Puddinu, Sabrina Casella, Egle Radice, Sylvia Thelen, Stefan Dirnhofer, Francesco Bertoni and Marcus Thelen _

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Oncotarget. 2017; 8:85068-85084. https://doi.org/10.18632/oncotarget.18844

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Abstract

Viola Puddinu1,2,*, Sabrina Casella1,2,*, Egle Radice1,2, Sylvia Thelen1, Stefan Dirnhofer3, Francesco Bertoni4 and Marcus Thelen1

1Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland

2Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland

3Institute of Pathology, University Hospital, University of Basel, Basel, Switzerland

4Institute of Oncology Research, Bellinzona, Switzerland

*These authors have contributed equally to this work

Correspondence to:

Marcus Thelen, email: marcus.thelen@irb.usi.ch

Keywords: ACKR3, CXCR4, chemokine, B cell, lymphoma

Received: December 20, 2016     Accepted: June 05, 2017     Published: June 29, 2017

ABSTRACT

Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma accounting for more than the 30% of the cases. Involvement of extranodal sites, such as bone marrow and central nervous system, is associated with poor prognosis. A contribution of the chemokine system in these processes is assumed as it is known as a critical regulator of the metastatic process in cancer. The atypical chemokine receptor 3 (ACKR3), which does not couple to G-proteins and does not mediate cell migration, acts as a scavenger for CXCL11 and CXCL12, interfering with the tumor homing CXCL12/CXCR4 axis. Here, functional expression of ACKR3 in DLBCL cells was necessary for colonization of the draining lymph node in an in vivo subcutaneous lymphoma model. Moreover, in a disseminated in vivo lymphoma model, ACKR3 expression was required for bone marrow and brain invasion and local tumor growth. The present data unveil ACKR3 as potential therapeutic target for the control of tumor dissemination in DLBCL.


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