Expression of functional interleukin-3 receptors on Hodgkin and Reed-Sternberg cells

Am J Pathol. 2002 Feb;160(2):585-96. doi: 10.1016/S0002-9440(10)64878-X.

Abstract

The human interleukin-3 receptor (IL-3R) is a heterodimeric complex consisting of an IL-3-specific alpha chain (IL-3Ralpha) and a common beta chain (beta(c)), this latter shared with the receptors for granulocyte-macrophage colony-stimulating factor and IL-5. Despite extensive research on cytokine circuitries regulating proliferation and survival of tumor cells in Hodgkin's disease (HD) the functional expression of IL-3Rs in this pathobiological entity has not yet been investigated. In the present study, we demonstrate that the great majority (>90%) of malignant Hodgkin and Reed-Sternberg cells of classic HD (19 of 19 analyzed cases) express IL-3Ralpha by immunostaining of frozen sections and cell suspensions from involved lymph nodes. Accordingly, HD cell lines (L428, KMH2, HDLM2, L1236) expressed the alpha and beta chains of IL-3R both at the mRNA and protein level, with a molecular size of IL-3Ralpha identical (70 kd) to that expressed by human myeloid cells. Exogenous IL-3 promoted the growth of cultured Hodgkin and Reed-Sternberg cells, such effect being potentiated by IL-9 co-stimulation, and was able to partially rescue tumor cells from apoptosis induced by serum deprivation. This data suggests an involvement of IL-3/IL-3R interactions in the cellular growth of HD through paracrine mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Division / drug effects
  • Cell Division / physiology
  • Flow Cytometry
  • Hodgkin Disease / immunology*
  • Hodgkin Disease / pathology
  • Humans
  • Immunohistochemistry
  • Interleukin-3 / genetics
  • Interleukin-3 / metabolism*
  • Interleukin-3 / pharmacology
  • Lymph Nodes / pathology
  • Receptors, Interleukin-3 / genetics
  • Receptors, Interleukin-3 / metabolism*
  • Reed-Sternberg Cells / immunology*
  • Reed-Sternberg Cells / pathology
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay
  • fas Receptor / metabolism

Substances

  • Interleukin-3
  • Receptors, Interleukin-3
  • fas Receptor