Direct influences of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) on the proliferation and cell surface antigen expression of cancer cells

Direct influences of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) on the proliferation and cell surface antigen expression of cancer cells
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DOI:
10.1006/cyto.1998.0504
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发表时间:
2000-01-01
期刊:
影响因子:
3.8
通讯作者:
Ichinose, Y
Ichinose, Y
中科院分区:
医学3区
文献类型:
--
作者:
Kuninaka, S;Yano, T;Ichinose, Y

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通过手术干预或非特异性免疫疗法产生的促炎细胞因子,例如白细胞介素1(IL-1)、肿瘤坏死因子α(TNF-α)、IL-6可直接影响肿瘤细胞的生长和转移。因此,阐明促炎性细胞因子对肿瘤细胞的直接影响,以获得更好的抗肿瘤治疗知识是非常重要的。使用四种人肺癌细胞系。将肿瘤细胞在各种浓度的IL-1 β、TNF-α或IL-6存在下孵育72小时,然后通过MTT测定评估增殖反应。用每种促炎细胞因子培养14天后,通过免疫细胞化学染色法评估细胞表面抗原表达(HLA-I类、HLA-IT类、CEA、唾液酸刘易斯(x))。在肿瘤细胞(PC-9、PC-12、QG-56、QG-95)和细胞因子(IL-1 β、TNF-α、IL-6)的各种组合中,仅TNF-α显著地表现出针对PC-9细胞的抗增殖作用。然而,观察到细胞因子对细胞表面抗原表达的各种调节。PC-9的HLA-I类抗原表达被TNF-α或IL-1 β增强。此外,IL-1 β能够诱导PC-9、QG-56和QG-95细胞中的CEA,而TNF-α能够增强QG-95细胞中唾液酸化Lewisx的表达。虽然促炎细胞因子对肿瘤细胞生长的影响很小,但对细胞表面抗原表达的一些调节是显著的。因此,HLA-I类表达的增强可以改善肿瘤细胞的免疫原性,而免疫原性的增强可以提高肿瘤细胞的免疫原性。因此CEA或唾液酸刘易斯(x)的诱导可能与促进转移有关。(C)北京大学出版社.
Pro-inflammatory cytokines, e.g. interleukin 1 (IL-1), tumour necrosis factor alpha (TNF-alpha), IL-6 produced by surgical intervention or non-specific immunotherapy may directly affect both the growth and the metastasis of tumour cells. It is therefore important to clarify the direct influence of pro-inflammatory cytokines on tumour cells in order to obtain abetter knowledge of anti-tumour therapy. Four human lung cancer cell lines were used. The tumour cells were incubated for 72 h in the presence of various concentrations of IL-1 beta, TNF-alpha, or IL-6 and then the proliferative response was assessed by an MTT assay. After 14 days of culture with each pro-inflammatory cytokine, the cell-surface antigen expressions (HLA-class I, HLA-class IT, CEA, sialyl Lewis(x)) were assessed by an immunocytochemical Staining method. Among the various combinations of tumour cells (PC-9, PC-12, QG-56, QG-95) and cytokines (IL-1 beta, TNF-alpha, IL-6), only TNF-alpha significantly exhibited an antiproliferative effect against PC-9 cells. However, various modulations of the cell-surface antigen expression by the cytokines were observed. The HLA-class I antigen expression of PC-9 was augmented by either TNF-alpha or IL-1 beta. Furthermore, IL-1 beta was able to induce CEA in PC-9, QG-56; and QG-95 cells while TNF-a was able to enhance the expression of sialyl Lewisx in QG-95 cells. Although the influence of pro-inflammatory cytokines on the growth of tumour cells was only slight, some modulations of the cell-surface antigen expression were notable. The augmentation of HLA-class I expression can thus improve the immunogenicity of tumour cells while the. induction of CEA or sialyl Lewis(x) may therefore be associated with the promotion of metastasis. (C) 2000 Academic Press.