Expression of functional interleukin-3 receptors on Hodgkin and Reed-Sternberg cells.
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.
Aldinucci
Donatella
D
Clinical & Experimental Hematology Research Unit, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale Tumori, via Pedemontana Occidentale 12, Aviano I-33081, Italy. daldinucci@cro.it
Poletto
Dalisa
D
Gloghini
Annunziata
A
Nanni
Paola
P
Degan
Massimo
M
Perin
Tiziana
T
Ceolin
Paola
P
Rossi
Francesca Maria
FM
Gattei
Valter
V
Carbone
Antonino
A
Pinto
Antonio
A
D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007377:Interleukin-3 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008198:Lymph Nodes / Q000473:pathology; D016185:Receptors, Interleukin-3 / Q000235:genetics / Q000378:metabolism*; D016539:Reed-Sternberg Cells / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D019014:fas Receptor / Q000378:metabolism
D007377:Interleukin-3; D016185:Receptors, Interleukin-3; D019014:fas Receptor