Cytokine production of lung cancer cell lines:: Correlation between their production and the inflammatory/immunological responses both in vivo and in vitro
Cytokine production of lung cancer cell lines:: Correlation between their production and the inflammatory/immunological responses both in vivo and in vitro
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DOI：
10.1111/j.1349-7006.2007.00507.x
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发表时间：
2007-07-01
期刊：
影响因子：
5.7
通讯作者：
Yasumoto, Kosei
中科院分区：
文献类型：
--
作者：
Fukuyama, Takashi;Ichiki, Yoshinobu;Yasumoto, Kosei
肿瘤细胞产生的细胞因子对抗肿瘤免疫应答和肿瘤生长具有多种作用。在本研究中，31个肺癌细胞系的细胞因子的生产进行了评估，而任何与组织学类型的相关性，在体外诱导肿瘤特异性细胞毒性T淋巴细胞（CTL），血管生成和炎症细胞浸润的肿瘤组织也进行了检查。使用酶联免疫吸附测定法测量培养物上清液中白细胞介素（IL）-1 α、IL-1 β、IL-4、IL-6、IL-8、IL-10、肿瘤坏死因子（TNF）-α、粒细胞巨噬细胞集落刺激因子（GM-CSF）、粒细胞集落刺激因子、转化生长因子（TGF）-β和血管内皮生长因子（VEGF）的产生。每种细胞因子在大量的肿瘤细胞系中产生。特别地，IL-6、IL-8、TGF-β和VEGF分别在31个细胞系中的18个（55%）、29个（94%）、31个（100%）和28个（90%）中产生。然而，任何肿瘤细胞系都不产生IL-4或TNF-α。TGF-β的产生在腺癌中显著高于鳞状细胞癌（P = 0.03）。免疫组织化学染色显示巨噬细胞浸润的程度，手术切除的肿瘤组织标本中的血管生成与相应细胞系的GM-CSF和IL-8产生密切相关。在六种肺癌细胞系中，在产生较低量的TGF-β（< 100 pg/mL）的三种肺癌细胞系中诱导CTL。这些结果表明，肿瘤细胞产生的TGF-β在体外可抑制CTL的诱导。本研究结果提示，肿瘤细胞产生的多种细胞因子可能在体内和体外发挥多种旁分泌效应。
Cytokines produced by tumor cells may have various effects on antitumor immune responses and tumor growth. In the present study, the cytokine production of 31 lung cancer cell lines was evaluated, while any correlation with the histological type, the induction of tumor-specific cytotoxic T lymphocytes (CTL) in vitro, and angiogenesis and the infiltration of inflammatory cells in tumor tissues were also examined. Production of interleukin (IL)-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, granulocyte macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor, transforming growth factor (TGF)-beta and vascular endothelial growth factor (VEGF) in the culture supernatant was measured using enzyme-linked immunosorbent assay. Each cytokine was produced in a substantial number of the tumor cell lines. In particular, IL-6, IL-8, TGF-beta and VEGF were produced in 18 (55%), 29 (94%), 31 (100%) and 28 (90%) of 31 cell lines, respectively. However, neither IL-4 nor TNF-alpha was produced at all by any tumor cell line. TGF-beta production was significantly higher in adenocarcinoma than in squamous cell carcinoma (P = 0.03). Immunohistochemical staining revealed the magnitude of macrophage infiltration, and angiogenesis in surgically resected tumor tissue specimens correlated well with GM-CSF and IL-8 production from the corresponding cell lines. Among six lung cancer cell lines, CTL were induced in the three lung cancer cell lines that produced a lower amount of TGF-beta (< 100 pg/mL). These findings suggested that TGF-beta produced by tumor cells could inhibit the induction of CTL in vitro. The present results suggest that the production of various cytokines from tumor cells might exert various paracrine effects both in vivo and in vitro.