Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration

Blood. 2001 Jul 15;98(2):428-35. doi: 10.1182/blood.v98.2.428.

Abstract

Multiple myeloma (MM) remains incurable, with a median survival of 3 to 4 years. This study shows direct effects of vascular endothelial growth factor (VEGF) upon MM and plasma cell leukemia (PCL) cells. The results indicate that VEGF triggers tumor cell proliferation via a protein kinase C (PKC)-independent Raf-1-MEK-extracellular signal-regulated protein kinase pathway, and migration via a PKC-dependent pathway. These observations provide the framework for novel therapeutic strategies targeting VEGF signaling cascades in MM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division / drug effects*
  • Cell Movement / drug effects*
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism
  • Endothelial Growth Factors / pharmacology*
  • Extracellular Matrix Proteins / analysis
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Flavonoids / pharmacology
  • Gene Expression
  • Humans
  • Leukemia, Plasma Cell / metabolism
  • Leukemia, Plasma Cell / pathology
  • Lymphokines / genetics
  • Lymphokines / metabolism
  • Lymphokines / pharmacology*
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • Protein Kinase C / metabolism
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Proto-Oncogene Proteins c-raf / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Extracellular Matrix Proteins
  • Flavonoids
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one