Involvement of the Syk-mTOR pathway in follicular lymphoma cell invasion and angiogenesis
| Autor: | Loic Ysebaert, Séverine Fruchon, T. Al Saati, Ludivine Leseux, Christine Bezombes, S Kheirallah, Jean-Jacques Fournié, Camille Laurent, Guy Laurent |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research Angiogenesis Follicular lymphoma Syk Biology Fostamatinib chemistry.chemical_compound Mice Phosphatidylinositol 3-Kinases Cell Line Tumor medicine Animals Humans Syk Kinase Neoplasm Invasiveness Lymphoma Follicular PI3K/AKT/mTOR pathway Neovascularization Pathologic TOR Serine-Threonine Kinases Intracellular Signaling Peptides and Proteins Hematology Protein-Tyrosine Kinases medicine.disease Lymphoma Vascular endothelial growth factor Oncology chemistry Matrix Metalloproteinase 9 Cancer research Tyrosine kinase Proto-Oncogene Proteins c-akt medicine.drug Signal Transduction |
| Zdroj: | Leukemia. 26(4) |
| ISSN: | 1476-5551 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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