Bone marrow fibroblasts induce expression of PI3K/NF-kappaB pathway genes and a pro-angiogenic phenotype in CLL cells

Leuk Res. 2008 Oct;32(10):1565-72. doi: 10.1016/j.leukres.2008.03.003. Epub 2008 Apr 14.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenic Proteins / metabolism*
  • Animals
  • Apoptosis
  • Bone Marrow Cells / cytology
  • Cell Communication
  • Cell Cycle / genetics
  • Cell Line
  • Coculture Techniques
  • DNA Repair / genetics
  • Fibroblasts / physiology*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / enzymology
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Mice
  • NF-kappa B / metabolism*
  • Phenotype
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Signal Transduction / genetics
  • Stromal Cells / physiology
  • Tumor Cells, Cultured

Substances

  • Angiogenic Proteins
  • NF-kappa B
  • Phosphatidylinositol 3-Kinases