Phospho-proteomic Analysis of Mantle Cell Lymphoma Cells Suggests a Pro-survival Role of B-cell Receptor Signaling

Overview

Journal Cell Oncol (Dordr)

Publisher Springer

Date 2011 Mar 12

PMID 21394647

Citations 37

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 Zamo

Affiliations

Soon will be listed here.

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.

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