Toll-like receptor 1/2 and 5 ligands enhance the expression of cyclin D1 and D3 and induce proliferation in mantle cell lymphoma

Mastorci, Katy, Muraro, Elena, Pasini, Elisa, Furlan, Chiara, Sigalotti, Luca, Cinco, Marina, Dolcetti, Riccardo and Fratta, Elisabetta (2016) Toll-like receptor 1/2 and 5 ligands enhance the expression of cyclin D1 and D3 and induce proliferation in mantle cell lymphoma. Plos One, 11 4: . doi:10.1371/journal.pone.0153823


Author Mastorci, Katy
Muraro, Elena
Pasini, Elisa
Furlan, Chiara
Sigalotti, Luca
Cinco, Marina
Dolcetti, Riccardo
Fratta, Elisabetta
Title Toll-like receptor 1/2 and 5 ligands enhance the expression of cyclin D1 and D3 and induce proliferation in mantle cell lymphoma
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2016-04-28
Year available 2016
Sub-type Article (original research)
DOI 10.1371/journal.pone.0153823
Open Access Status DOI
Volume 11
Issue 4
Total pages 17
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Abstract Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin’s lymphoma with a still undefined etiology. Several lines of evidence are consistent with the possible involvement of peculiar microenvironmental stimuli sustaining tumor cell growth and survival, as the activation of Toll-like receptors (TLR) 4 and 9. However, little is known about the contribution of other TLRs of pathogenic relevance in the development of MCL. This study reports evidence that MCL cell lines and primary MCL cells express different levels of TLR2 and TLR5, and that their triggering is able to further activate the Akt, MAPK, and NF-κB signaling cascades, known to be altered in MCL cells. This leads to the enhancement of cyclin D1 and D3 over-expression, occurring at post-translational level through a mechanism that likely involves the Akt/GSK-3α/β pathway. Interestingly, in primary B cells, TLR1/2 or TLR5 ligands increase protein level of cyclin D1, which is not usually expressed in normal B cells, and cyclin D3 when associated with CD40 ligand (CD40L), IL-4, and anti-human-IgM co-stimulus. Finally, the activation of TLR1/2 and TLR5 results in an increased proliferation of MCL cell lines and, in the presence of co-stimulation with CD40L, IL-4, and anti-human-IgM also of primary MCL cells and normal B lymphocytes. These effects befall together with an enhanced IL-6 production in primary cultures. Overall, our findings suggest that ligands for TLR1/2 or TLR5 may provide critical stimuli able to sustain the growth and the malignant phenotype of MCL cells. Further studies aimed at identifying the natural source of these TLR ligands and their possible pathogenic association with MCL are warranted in order to better understand MCL development, but also to define new therapeutic targets for counteracting the tumor promoting effects of lymphoma microenvironment.
Keyword Non-Hodgkin lymphoma
Nf-kappa B
Borrelia burgdorferi
Human monocytes
Activation
Infection
Pathways
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
 
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