Hodgkin and Reed-Sternberg cells express functional c-kit receptors and interact with primary fibroblasts from Hodgkin's disease-involved lymph nodes through soluble and membrane-bound stem cell factor

Donatella Aldinucci, Dalisa Poletto, Paola Nanni, Massimo Degan, Annunziata Gloghini, Raffaele Di Francia, Stefania Russo, Antonino Carbone, Antonio Pinto, Valter Gattei

Research output: Contribution to journalArticlepeer-review

Abstract

Classic Hodgkin's disease (cHD) is a lymphoid neoplasia characterized by few malignant Hodgkin and Reed-Sternberg (H-RS) cells, embedded in an abundant background of non-tumour cells. We have previously demonstrated the expression in primary H-RS cells of the receptor tyrosine kinase (RTK) c-kit; here we describe its functional role in the cross-talk between H-RS cells themselves with neighbouring cell populations. In particular, we analysed the expression of c-kit and its ligand stem cell factor (SCF) in a panel of HD-derived cell lines and fibroblasts from HD-involved lymph nodes (HDF). While c-kit was expressed by HD-derived cell lines, usually in the absence of SCF, this latter molecule, in its soluble and/or membrane-bound (mb) form, was in turn expressed at a high level by primary HDF. In vitro adhesion between HD-derived cell lines and HDF was mainly mediated by c-kit/SCF interactions, and this phenomenon was significantly inhibited by an excess of soluble SCF or by neutralizing anti-c-kit monoclonal antibodies. Furthermore, both soluble and mb-SCF increased growth and colony survival of HD-derived cell lines; these effects were significantly enhanced upon co-stimulation of H-RS cells with interleukin 9. Finally, soluble SCF was able to partially rescue H-RS cells from apoptosis induced by serum starvation. Taken together, our data indicated the expression of functional c-kit receptor by H-RS cells and suggests a role of SCF in the pathobiology of cHD.

Original languageEnglish
Pages (from-to)1055-1064
Number of pages10
JournalBritish Journal of Haematology
Volume118
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • c-kit
  • Cytokine receptors
  • Hodgkin cells
  • Reed-Sternberg cells
  • Stem cell factor

ASJC Scopus subject areas

  • Hematology

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