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.
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.
Clinical and Experimental Haematology Research Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Istituto Nazionale Tumori, Aviano, Italy. daldinucci@cro.it
Donatella
D
Aldinucci
Dalisa
D
Poletto
Paola
P
Nanni
Massimo
M
Degan
Annunziata
A
Gloghini
Raffaele
R
Di Francia
Stefania
S
Russo
Antonino
A
Carbone
Antonio
A
Pinto
Valter
V
Gattei
D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion; D018920:Coculture Techniques; D005347:Fibroblasts / Q000378:metabolism*; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016906:Interleukin-9 / Q000494:pharmacology; D008198:Lymph Nodes; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000378:metabolism*; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D019089:Stem Cell Factor / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016906:Interleukin-9; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit