Hepatocyte growth factor promotes migration of human myeloma cells

Haematologica. 2008 Apr;93(4):619-22. doi: 10.3324/haematol.11867. Epub 2008 Mar 6.

Abstract

Multiple myeloma is characterized by the accumulation and dissemination of malignant plasma cells in the bone marrow. Cell migration is thought to be important for these events. We studied migration in a Transwell two-chamber assay and tested the motogenic effect of various cytokines. In addition to insulin-like growth factor-1 and stromal cell-derived growth factor-1alpha, previously known as chemoattractants for myeloma cells, we identified hepatocyte growth factor as a potent attractant for myeloma cells. Hepatocyte growth factor-mediated migration was dependent on phosphatidylinositol-3-kinase, involved the MAPK/Erk signaling cascade and VLA-4 integrins, but did not involve Akt, mTOR or G proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow / pathology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / pathology
  • Chemokine CXCL12 / physiology
  • Chemotaxis / drug effects*
  • Cytokines / pharmacology
  • Enzyme Inhibitors / pharmacology
  • GTP-Binding Proteins / analysis
  • Hepatocyte Growth Factor / pharmacology*
  • Hepatocyte Growth Factor / physiology
  • Humans
  • Indoles / pharmacology
  • Integrin alpha4beta1 / physiology
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Multiple Myeloma / pathology*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / physiology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Plasma Cells / drug effects*
  • Plasma Cells / pathology
  • Protein Kinases / analysis
  • Proto-Oncogene Proteins c-akt / analysis
  • Proto-Oncogene Proteins c-met / physiology
  • Recombinant Proteins / pharmacology
  • Sulfones / pharmacology
  • TOR Serine-Threonine Kinases
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / pathology

Substances

  • 5-((2,6-dichlorobenzyl)sulfonyl)-3-((3,5-dimethyl-4-((2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-1,3-dihydro-2H-indol-2-one
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Cytokines
  • Enzyme Inhibitors
  • HGF protein, human
  • Indoles
  • Integrin alpha4beta1
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Recombinant Proteins
  • Sulfones
  • Hepatocyte Growth Factor
  • Protein Kinases
  • MTOR protein, human
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • GTP-Binding Proteins