Expression of Interleukin-9 in Nasal Natural Killer/T-Cell Lymphoma Cell Lines and Patients

Abstract

Purpose: 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. Experimental Design: 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-likeT-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 innasal NK/T-cell lymphoma possibly via an autocrine mechanism.

Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro

“…Only a few genome-wide profiling studies using NK-cell lines 13,14 and a limited number of NK-cell 15 and gd T-cell lymphoma cases have been performed. 16 In this study, we have defined molecular signatures for ENKTL and related malignancies.…”

Soluble ICAM-1 secretion and its functional role as an autocrine growth factor in nasal NK/T cell lymphoma cells

“…We have previously shown that SNK6 cells produce several cytokines and chemokines such as interferon (IFN)-γ, interleukin (IL)-9, IL-10 and interferon-γ-inducible protein (IP)-10, which play roles in cellular proliferation and invasion in an autocrine manner [7][8][9]. Furthermore, monocytes attracted by IP-10 enhance the proliferation via cell-to-cell contact [10].…”

Interleukin-17 inhibits development of malignant pleural effusion via interleukin-9-dependent mechanism

“…Consistent with our previous findings (Lin et al, 2014), we confirmed that IL-17 deficiency promoted MPE formation by enhancing the angiogenesis and proliferation of pleural tumors, and that in vivo administration of anti-IL-17 mAb in WT mice was able to promote MPE formation by increasing tumor angiogenesis and proliferation, while in vivo administration of rmIL-17 in IL-17 / mice was able to inhibit MPE formation by diminishing tumor angiogenesis and proliferation. Previous studies have suggested that IL-9 plays an important role in NK/T-cell lymphoma possibly via an autocrine mechanism (Nagato et al, 2005). Purwar and colleagues (Purwar et al, 2012) have demonstrated that that mice deficient in Th17 cell development have substantial resistance to melanoma growth in a IL-9-dependent manner; and treatment with exogenous IL-9 inhibits tumor growth in vivo.…”