The biological sequelae of stromal cell-derived factor-1alpha in multiple myeloma

Teru Hideshima, Dharminder Chauhan, Toshiaki Hayashi, Klaus Podar, Masaharu Akiyama, Deepak Gupta, Paul Richardson, Nikhil Munshi, Kenneth C Anderson

Research output: Journal article (peer-reviewed)Journal article

161 Citations (Scopus)

Abstract

Stromal cell-derived factor (SDF)-1alpha mediates migration of normal hematopoietic stem cells, but its role in hematological malignancies is undefined. In this study, we detected SDF-1alpha in bone marrow (BM) plasma from 10 patients with MM (multiple myeloma; 2.6 +/- 1.5 ng/ml) and BM stromal cell culture supernatants from 5 patients with MM (0.6 +/- 0.2 ng/ml). We show that SDF-1alpha promotes proliferation, induces migration, and protects against dexamethasone-induced apoptosis in MM cells, but these effects are only modest. In MM cell lines and patient MM cells, SDF-1alpha induces phosphorylation of p42/44 mitogen-activated protein kinase, as well as Akt and its downstream target Bad, and also activates nuclear factor-kappaB. In the BM milieu, SDF-1alpha up-regulates secretion of interleukin 6 and vascular endothelial growth factor in BM stromal cells, which promote tumor cell growth, survival, and migration. These data demonstrate that SDF-1alpha promotes growth, migration and drug resistance of MM cells in the BM microenvironment, but these effects are only modest, SDF-1alpha therefore does not represent a target for novel therapeutics in this disease.

Original languageEnglish
Pages (from-to)539-544
Number of pages6
JournalMolecular Cancer Therapeutics
Volume1
Issue number7
Publication statusPublished - May 2002
Externally publishedYes

Keywords

  • Apoptosis
  • Blotting, Western
  • Bone Marrow/metabolism
  • Bone Marrow Cells/metabolism
  • Carrier Proteins/metabolism
  • Cell Division
  • Cell Movement
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC/metabolism
  • DNA/biosynthesis
  • Dexamethasone/pharmacology
  • Dose-Response Relationship, Drug
  • Endothelial Growth Factors/metabolism
  • Flow Cytometry
  • Humans
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Interleukin-6/metabolism
  • Lymphokines/metabolism
  • Multiple Myeloma/metabolism
  • NF-kappa B/metabolism
  • Phosphorylation
  • Signal Transduction
  • Time Factors
  • Up-Regulation
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • bcl-Associated Death Protein

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