Evidence for cell adhesion-mediated drug resistance of multiple myeloma cells in vivo

Int J Biol Markers. Oct-Dec 2006;21(4):218-22.

Abstract

Background/aims: Multiple myeloma is an incurable disease and patients eventually die of disease progression due to drug resistance. VLA-4 (very late antigen 4), VCAM (vascular adhesion molecule), LFA-1 (leukocyte function-associated antigen 1), and ICAM-1 (intercellular adhesion molecule 1)-mediated adhesion of myeloma cells to bone marrow stromal cells induces primary multidrug resistance in vitro. Based on these preclinical data we hypothesized that myeloma cells with strong adhesion - due to strong expression of adhesion molecules on the cell surface - are selected by chemotherapy in patients. To prove this hypothesis we determined the expression levels of adhesion molecules in 31 multiple myeloma patients by flow cytometry.

Methods: A 3-color stain with CD38, CD138 and antibodies against VLA-4, ICAM-1, LFA-1, and VCAM was performed. The patients were either at diagnosis (chemo-naive; n=17) or at relapse (pre-treated; n=15). Furthermore, the response to the next chemotherapy of chemo-naive patients was correlated with the expression levels of adhesion molecules.

Results: ICAM-1, VLA-4, and VCAM expression was higher in pre-treated patients than in chemo-naive patients and the expression levels increased with the number of chemotherapy regimens. Primarily multidrug-resistant patients had significantly higher expression levels of VLA-4 and ICAM-1 than responders.

Conclusion: This study suggests that multiple myeloma cells expressing high levels of VLA-4 and ICAM-1 are drug resistant and that such a subpopulation of cells is selected by chemotherapy.

MeSH terms

  • ADP-ribosyl Cyclase 1 / analysis
  • Cell Adhesion
  • Cell Adhesion Molecules / analysis*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Integrin alpha4beta1 / analysis
  • Intercellular Adhesion Molecule-1 / analysis
  • Lymphocyte Function-Associated Antigen-1 / analysis
  • Male
  • Membrane Glycoproteins / analysis
  • Middle Aged
  • Multiple Myeloma / chemistry
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Syndecan-1 / analysis
  • Vascular Cell Adhesion Molecule-1 / analysis

Substances

  • Cell Adhesion Molecules
  • Integrin alpha4beta1
  • Lymphocyte Function-Associated Antigen-1
  • Membrane Glycoproteins
  • SDC1 protein, human
  • Syndecan-1
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1