Direct influences of pro-inflammatory cytokines (IL-1beta, TNF-alpha, IL-6) on the proliferation and cell-surface antigen expression of cancer cells.
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 a better 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-1beta, 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 II, 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-1beta, 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-1beta. Furthermore, IL-1beta was able to induce CEA in PC-9, QG-56, and QG-95 cells while TNF-alpha was able to enhance the expression of sialyl Lewis(x)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.
Kuninaka
S
S
Department of Chest Surgery, National Kyushu Cancer Center, Fukuoka, Japan.
Yano
T
T
Yokoyama
H
H
Fukuyama
Y
Y
Terazaki
Y
Y
Uehara
T
T
Kanematsu
T
T
Asoh
H
H
Ichinose
Y
Y
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D000704:Analysis of Variance; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D000954:Antigens, Surface / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006680:HLA Antigens / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D016207:Cytokines; C042317:DU-PAN-2 antigen, human; D006680:HLA Antigens; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha