Production of interferon-{gamma}-inducible protein-10 and its role as an autocrine invasion factor in nasal natural killer/T-cell lymphoma cells.
OBJECTIVE
Nasal natural killer (NK)/T-cell lymphoma is associated with Epstein-Barr virus and has poor prognosis because of local invasion and/or multiple dissemination. Recently, the role of chemokines/chemokine receptors in tumor proliferation and invasion has been shown. In this study, we examined whether the specific chemokines were related to the tumor behaviors in nasal NK/T-cell lymphoma.


METHODS
A chemokine protein array was used to examine specific chemokines produced by SNK-6 and SNT-8 (Epstein-Barr virus-positive nasal NK/T-cell lymphoma lines). The expression of interferon gamma-inducible protein 10 (IP-10) and the IP-10 receptor CXCR3 was investigated by ELISA and flow cytometry. Cell growth and invasion were assessed by the MTT and Matrigel invasion assays, respectively. Immunohistologic staining and ELISA were used to examine IP-10 expression in biopsies and sera from patients, respectively.


RESULTS
IP-10 was specifically produced by SNK-6 and SNT-8. Moreover, CXCR3 was expressed on the NK cell lines. Functionally, IP-10 did not affect cell proliferation but enhanced cell invasion. In biopsy samples, IP-10 and CXCR3 expressions were detected in the lymphoma cells. Serum IP-10 levels in the patients were much higher than those of healthy controls and the levels were decreased during the complete remission phase after treatments.


CONCLUSIONS
These results suggest that IP-10 may play an important role in cell invasion in nasal NK/T-cell lymphoma through an autocrine mechanism.
Moriai
Shigetaka
S
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Asahikawa, Japan.
Takahara
Miki
M
Ogino
Takeshi
T
Nagato
Toshihiro
T
Kishibe
Kan
K
Ishii
Hideyuki
H
Katayama
Akihiro
A
Shimizu
Norio
N
Harabuchi
Yasuaki
Y
D000328:Adult; D000368:Aged; D001706:Biopsy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054357:Chemokine CXCL10 / Q000096:biosynthesis*; D018925:Chemokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012074:Remission Induction
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines