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Published in: Cellular Oncology 2/2011

Open Access 01-04-2011 | Original Paper

Phospho-proteomic analysis of mantle cell lymphoma cells suggests a pro-survival role of B-cell receptor signaling

Authors: Chiara Pighi, Ting-Lei Gu, Irene Dalai, Stefano Barbi, Claudia Parolini, Anna Bertolaso, Serena Pedron, Alice Parisi, Jianmin Ren, Daniela Cecconi, Marco Chilosi, Fabio Menestrina, Alberto Zamò

Published in: Cellular Oncology | Issue 2/2011

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Abstract

Background

Mantle cell lymphoma (MCL) is currently an incurable entity, and new therapeutic approaches are needed. We have applied a high-throughput phospho-proteomic technique to MCL cell lines to identify activated pathways and we have then validated our data in both cell lines and tumor tissues.

Methods

PhosphoScan analysis was performed on MCL cell lines. Results were validated by flow cytometry and western blotting. Functional validation was performed by blocking the most active pathway in MCL cell lines.

Results

PhosphoScan identified more than 300 tyrosine-phosporylated proteins, among which many protein kinases. The most abundant peptides belonged to proteins connected with B-cell receptor (BCR) signaling. Active BCR signaling was demonstrated by flow cytometry in MCL cells and by western blotting in MCL tumor tissues. Blocking BCR signaling by Syk inhibitor piceatannol induced dose/time-dependent apoptosis in MCL cell lines, as well as several modifications in the phosphorylation status of BCR pathway members and a collapse of cyclin D1 protein levels.

Conclusion

Our data support a pro-survival role of BCR signaling in MCL and suggest that this pathway might be a candidate for therapy. Our findings also suggest that Syk activation patterns might be different in MCL compared to other lymphoma subtypes.
Appendix
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Metadata
Title
Phospho-proteomic analysis of mantle cell lymphoma cells suggests a pro-survival role of B-cell receptor signaling
Authors
Chiara Pighi
Ting-Lei Gu
Irene Dalai
Stefano Barbi
Claudia Parolini
Anna Bertolaso
Serena Pedron
Alice Parisi
Jianmin Ren
Daniela Cecconi
Marco Chilosi
Fabio Menestrina
Alberto Zamò
Publication date
01-04-2011
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 2/2011
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-011-0019-7

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