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

Abstract

Summary. 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.