Expression of CCL5/RANTES by Hodgkin and Reed-Sternberg cells and its possible role in the recruitment of mast cells into lymphomatous tissue.
HL is a malignant lymphoma characterized by a small number of malignant HRS cells among a major population of infiltrating reactive cells, e.g., lymphocytes and eosinophils. We previously reported that mast cells are present in HL-affected lymph nodes and therein are the predominant CD30L-expressing cells. The CD30L expressed on mast cells is functionally active and can provide stimulatory signals to HRS cells. Thus, mast cells constitute an important portion of the infiltrating reactive cells that contribute to tumor progression in HL. Control of the recruitment of this previously unrecognized cell and its interactions with tumor cells are essentially unknown. To elucidate if mast cells might be specifically attracted to the tumor area by chemokines produced by HRS cells, we investigated chemokine expression in HL cell lines and in vivo. By RNase protection assay, mRNA expression of several chemokines could be detected in the cell lines. Despite the heterogeneous expression profile exhibited by the cell lines, 4 of 5 expressed CCL5 (RANTES) mRNA. RT-PCR and immunohistochemistry confirmed expression of CCL5 in vivo. Furthermore, secreted CCL5 was detected in conditioned media from 3 of the cell lines. In a migration assay, we found that CCL5 present in conditioned medium could induce mast cell migration. Taken together, our results suggest that CCL5 produced by HRS cells is one mechanism by which mast cells can be attracted into the tumor tissue in HL.
Fischer
Marie
M
Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden.
Juremalm
Mikael
M
Olsson
Niclas
N
Backlin
Carin
C
Sundström
Christer
C
Nilsson
Kenneth
K
Enblad
Gunilla
G
Nilsson
Gunnar
G
D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D006689:Hodgkin Disease / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000473:pathology
D018946:Chemokine CCL5; D018925:Chemokines; D017931:DNA Primers; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D012259:Ribonuclease, Pancreatic