Bone marrow fibroblasts induce expression of PI3K/NF-kappaB pathway genes and a pro-angiogenic phenotype in CLL cells.
Microarray-based gene expression profiling (GEP) was used to study how stroma modulates the survival of CLL cells in an in vitro coculture model employing the murine fibroblast cell line M2-10B4. CLL cells cultured in direct contact with the stromal layer (STR) showed a significantly better survival than cells cultured in transwell (TW) inserts above the M2-10B4 cells. STR as compared to TW conditions induced a significant up-regulation of PI3K/NF-kappaB pro-survival pathway genes and mediated a pro-angiogenetic switch in the CLL cells by up-regulation of vascular endothelial growth factor (VEGF) and osteopontin (OPN) and down-regulation of the anti-angiogenetic molecule thrombospondin-1 (TSP-1).
Edelmann
J
J
Department of Hematology, University Hospital, University of Duisburg-Essen, Essen, Germany.
Klein-Hitpass
L
L
Carpinteiro
A
A
Führer
A
A
Sellmann
L
L
Stilgenbauer
S
S
Dührsen
U
U
Dürig
J
J
D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D002450:Cell Communication; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D018920:Coculture Techniques; D004260:DNA Repair / Q000235:genetics; D005347:Fibroblasts / Q000502:physiology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D017154:Stromal Cells / Q000502:physiology; D014407:Tumor Cells, Cultured
D042501:Angiogenic Proteins; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases