DIRECT INFLUENCES OF PRO-INFLAMMATORY CYTOKINES (IL-1β, TNF-α, IL-6) ON THE PROLIFERATION AND CELL-SURFACE ANTIGEN EXPRESSION OF CANCER CELLS

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2000-01, Vol.12 (1), p.8-11
• Main Authors: Kuninaka, Shinji, Yano, Tokujiro, Yokoyama, Hideki, Fukuyama, Yasuro, Terazaki, Yasuhiro, Uehara, Tadashi, Kanematsu, Takanori, Asoh, Hiroshi, Ichinose, Yukito
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - pathology; adhesion molecules/human lymphocyte antigen (HLA)/metastasis/pro-inflammatory cytokine/proliferation; Analysis of Variance; Antigens, Neoplasm - biosynthesis; Antigens, Surface - biosynthesis; Biomarkers, Tumor - biosynthesis; Carcinoembryonic Antigen - biosynthesis; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Cell Division; Cytokines - metabolism; Gene Expression Regulation, Neoplastic; HLA Antigens - biosynthesis; Humans; Immunohistochemistry; Interleukin-1 - metabolism; Interleukin-6 - metabolism; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.1998.0504

Pro-inflammatory cytokines, e.g. interleukin 1 (IL-1), tumour necrosis factor α (TNF-α), 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 a better knowledge of anti-tumour therapy. Four human lung cancer cell lines were used. The tumour cells were incubated for 72h in the presence of various concentrations of IL-1β, TNF-α, 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 II, CEA, sialyl Lewisx) 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-1β, TNF-α, IL-6), only TNF-α 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-α or IL-1β. Furthermore, IL-1β was able to induce CEA in PC-9, QG-56, and QG-95 cells while TNF-α was able to enhance the expression of sialyl Lewisxin 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 Lewisxmay therefore be associated with the promotion of metastasis.