<Original Article> Interleukin-6 Functions as An Autocrine Invasion Factor of Human Pancreatic Cancer Cells

It was reported that serum interleukin-6 (IL-6) levels were increased in pancreatic cancer patients. However, the relationship between IL-6 expression and invasion of the pancreatic cancer has not yet been clarified. Therefore, the purpose of this study was to determine the effect of IL-6 on tumor cell invasion by the invasion in human pancreatic cancer cell line (PSN-1) and two sub-clones. High invasive clone (5H) and low invasive clone (5L) were established from wild type PSN-1 (WT) after five times passage of invasion assay. The invasive ability of PSN-1 cells was enhanced by IL-6 administration. The invasive ability of 5H cells was approximately two-folds higher than that of 5L cells and WT, and the level of IL-6 in the conditioned medium of 5H cells was significantly higher than those of 5L cells and WT. Furthermore, IL-6 receptor expression was observed in 70 %of 5H cells while it was expressed only in 33 %of 5L cells. 5H cells were spindle-shaped with long pseudopodia, while 5L cells were relatively round and pseudopodia formation was not observed. Endogenous IL-6 administration induced dose dependent enhancement of invasive ability both in 5H and 5L cells and conferred a spindle-like phenotype to 5L cells, but it did not affect on the cell proliferation in all 5H, 5L and WT cells. Conditioned medium from 5H cells (HCM) enhanced the invasive abilities of both 5H cells and 5L cells and conferred a spindle-like phenotype to 5L cells. The 5L cell-derived conditioned medium (LCM) also showed a similar effect on the invasive ability of both 5H and 5L cells. The effect of HCM on the invasive ability of 5H cells was partially inhibited by addition of anti-human IL-6 neutralizing antibody. In conclusion, overexpression of IL-6 and its receptor may contribute to the highly invasive characteristic of some pancreatic cancer cells, and these data raise the possibility that the regulation of IL-6 ligand/receptor interaction may prove useful in the therapy of this malignancy.