Expression of interleukin-9 in nasal natural killer/T-cell lymphoma cell lines and patients.
OBJECTIVE
Nasal natural killer (NK)/T-cell lymphoma is associated with EBV and has distinct clinical and histologic features. However, little is known about its genetic features. In this study, we examined the genes expressed by SNK-6 and SNT-8 cells, which were established from nasal NK/T-cell lymphomas, and found that interleukin (IL)-9 was specifically expressed in these two cell lines.


METHODS
cDNA array was used to examine the genes expressed by SNK-6 and SNT-8 cells. Expression of IL-9 and IL-9 receptor was investigated by reverse transcription-PCR, ELISA, and flow cytometry. Cell growth was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Immunohistologic staining and ELISA were used to examine IL-9 expression in biopsies and sera from patients, respectively.


RESULTS
In cDNA array, expression of IL-9 mRNA was much higher in SNK-6 and SNT-8 cells than in NK-92 cells from non-nasal NK-cell lymphoma and peripheral blood mononuclear cells from healthy volunteers. Furthermore, IL-9 was specifically expressed by SNK-6 and SNT-8 cells but not by other NK-cell, NK-like T-cell, and T-cell lymphoma/leukemia cell lines. IL-9 receptor was also expressed on the surfaces of SNK-6 and SNT-8 cells. An IL-9-neutralizing antibody inhibited the growth of these two cell lines, whereas recombinant human IL-9 enhanced their growth. Most significantly, IL-9 was present in biopsies and sera from patients with this lymphoma.


CONCLUSIONS
These results suggest that IL-9 plays an important role in nasal NK/T-cell lymphoma possibly via an autocrine mechanism.
Nagato
Toshihiro
T
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Asahikawa, Japan.
Kobayashi
Hiroya
H
Kishibe
Kan
K
Takahara
Miki
M
Ogino
Takeshi
T
Ishii
Hideyuki
H
Oikawa
Kensuke
K
Aoki
Naoko
N
Sato
Keisuke
K
Kimura
Shoji
S
Shimizu
Norio
N
Tateno
Masatoshi
M
Harabuchi
Yasuaki
Y
D019898:Autocrine Communication; D001706:Biopsy; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000473:pathology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D016906:Interleukin-9 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D009669:Nose Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics; D053651:Receptors, Interleukin-9; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
C508045:IL9R protein, human; D016906:Interleukin-9; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053651:Receptors, Interleukin-9