The expression of fibroblast growth factors and their receptors in Hodgkin's lymphoma.
The expression of fibroblast growth factors (FGF1 and FGF2) and their receptors has been reported in a variety of human neoplasms, including haematological neoplasia. Fibroblast growth factors can promote tumour growth directly, or indirectly through promoting the growth of vessels. In the present study, we evaluated the expression of FGF1 and FGF2 as well as FGF receptors 1-4 (FGFR1-FGFR4) in 39 cases of Hodgkin's lymphoma, including all subtypes, as well as Hodgkin's lymphoma cell lines. FGF1 and FGF2 and their receptors FGFR2-FGFR4, but not FGFR1, were found to be expressed by the malignant cells in the majority of cases. Interestingly, only FGFR3, but none of the FGFs or the other FGFRs, was expressed by the Hodgkin's lymphoma cell lines. This indicates that only FGFR3 is constitutively expressed by Hodgkin's lymphoma cells, whereas FGFs and the other FGFRs are induced in vivo. Culture of the Hodgkin's cell lines under conditions of hypoxic stress could induce vascular endothelial growth factor (VEGF) but not FGF expression. FGFs, in contrast to VEGF, might be expressed in response to paracrine stimuli. In situ hybridization did not reveal FGFR3 gene amplification or translocation as the cause of constitutive FGFR3 expression, as has been shown in a subset of multiple myeloma. FGFR3 might be expressed as part of the Hodgkin's cell phenotype. The demonstration of widespread expression of FGFs and some of their receptors in Hodgkin's lymphoma suggests that FGFs are important for sustaining growth of the lymphoma and suggests that anti-FGF antibodies could be used as an adjuvant treatment.
Khnykin
Denis
D
Department of Pathology, The Norwegian Radium Hospital, University of Oslo, Montebello, 0310 Oslo, Norway.
Troen
Gunhild
G
Berner
Jeanne-Marie
JM
Delabie
Jan
J
D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D016220:Fibroblast Growth Factor 1 / Q000032:analysis; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D005346:Fibroblast Growth Factors / Q000032:analysis*; D015870:Gene Expression; D006689:Hodgkin Disease / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000032:analysis; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000032:analysis; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000032:analysis; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3; D051499:Receptor, Fibroblast Growth Factor, Type 4