Document Detail

Involvement of the Syk-mTOR pathway in follicular lymphoma cell invasion and angiogenesis.
MedLine Citation:
PMID:  21926965     Owner:  NLM     Status:  MEDLINE    
Follicular lymphoma (FL) is the second-most common non-Hodgkin's lymphoma. The disease affects the lymph nodes, and 50% of patients present with bone marrow infiltration; however, the mechanisms involved in dissemination of the disease are not yet known. We previously reported that FL cells display an overexpression of Syk, a tyrosine kinase involved in many cellular processes including cell migration. Therefore, we sought to explore its role in the invasive process. Here, we show that FL patients display higher matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) levels than healthy donors. Moreover, using Syk small interfering RNA and the Syk inhibitor R406, we demonstrate that, in FL cells, Syk is involved in the regulation of MMP-9 and VEGF expression, and that invasion and angiogenesis is mediated through a phosphatidylinositol-3 kinase (PI3K)-mammalian target of rapamycin module. Finally, using a FL xenograft mouse model we observe that fostamatinib (R788), inhibits MMP-9 expression and angiogenesis in vivo. Altogether, this study provides strong evidence that Syk represents an encouraging therapeutic target in FL and suggests the potential use of fostamatinib as an anti-invasive and anti-angiogenic drug.
S Fruchon; S Kheirallah; T Al Saati; L Ysebaert; C Laurent; L Leseux; J J Fournié; G Laurent; C Bezombes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-16
Journal Detail:
Title:  Leukemia     Volume:  26     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-11     Completed Date:  2012-06-04     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  795-805     Citation Subset:  IM    
CRCT INSERM UMR1037, CNRS ERL5294, Universite Toulouse, CHU Purpan, Toulouse, France.
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MeSH Terms
Cell Line, Tumor
Intracellular Signaling Peptides and Proteins / physiology*
Lymphoma, Follicular / pathology*
Matrix Metalloproteinase 9 / genetics
Neoplasm Invasiveness
Neovascularization, Pathologic / etiology*
Phosphatidylinositol 3-Kinases / physiology
Protein-Tyrosine Kinases / physiology*
Proto-Oncogene Proteins c-akt / physiology
Signal Transduction / physiology*
TOR Serine-Threonine Kinases / physiology*
Vascular Endothelial Growth Factor A / physiology
Reg. No./Substance:
0/Intracellular Signaling Peptides and Proteins; 0/Vascular Endothelial Growth Factor A; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC protein, human; EC Serine-Threonine Kinases; EC Kinases; EC kinase; EC Proteins c-akt; EC Metalloproteinase 9

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