Oncotarget

Research Papers:

Improvement of the rituximab–induced cell death by potentiation of the store-operated calcium entry in mantle cell lymphoma cell lines

Isabelle Doignon, Olivier Fayol and Olivier Dellis

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Oncotarget. 2019; 10:4466-4478. https://doi.org/10.18632/oncotarget.27063

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Abstract

Isabelle Doignon1,2, Olivier Fayol1,2 and Olivier Dellis1,2

1 Interactions Cellulaires et Physiopathologie Hépatique, INSERM UMR-S 1174, Paris, France

2 Université Paris-Sud, Université Paris Saclay, Paris, France

Correspondence to:

Olivier Dellis,email: olivier.dellis@u-psud.fr

Keywords: mantle cell lymphoma; rituximab; store-operated calcium entry; potentiation; apoptosis

Received: December 08, 2018     Accepted: June 19, 2019     Published: July 09, 2019

ABSTRACT

Mantle Cell Lymphoma (MCL) is one of the worst lymphomas with a median overall survival of 3 to 4 years. Even if the use of rituximab was a great step in therapy, patients commonly develop resistance and relapse. New therapies or complement of existing therapies should be developed. Using spectrofluorimetry, we found that the resting cytosolic Ca2+ ion concentration [Ca2+]cyt of MCL patients cells and MCL cell lines was increased. This increase is correlated with a larger store-operated calcium entry (SOCE) amplitude which is responsible for the Ca2+ ions influx. Furthermore, using a SOCE potentiating agent, we demonstrated that in the MCL Rec-1 cell line, the SOCE is already activated in resting conditions. Interestingly, this potentiating agent alone, by disturbing the SOCE, induced the apoptosis of Rec-1 cells with the same efficacy than rituximab. The use of the potentiating agent in addition to rituximab strengthens the rituximab-induced apoptosis of rituximab-sensitive Granta-519 and Rec-1 cells. However, this potentiating agent cannot convert the Jeko-1 rituximab-resistant to a rituximab-sensitive cell line. Our results confirm that the use of compound acting on the Ca2+ homeostasis could be a new target of interest in complement to existing therapies.


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