Expression and function of interleukin-8 in human hepatocellular carcinoma

Expression and functions of interleukin (IL)-8, a pro-inflammatory cytokine with angiogenesis action, was examined in 23 surgically resected hepatocel lular carcinoma (HCC) specimens and 7 HCC cell lines. In all HCC tissues, I L-8 expression was confirmed with reverse-transcription polymerase chain re action method and enzyme-linked immunosorbent assay, and immunohistochemist ry showed HCC cells were the major producer of IL-8 in the tissues. Microve ssel density was measured by the double immunohistochemical staining of mus cular vessels in HCC tissues, but the density was not related to the level of IL-8 in the HCC tissues. On the other hand, in the co-culture of human u mbilical vein endothelial cells (HUVEC) and a HCC cell line (KIM-1), IL-8 p roduced by KIM-1 significantly accelerated the proliferation of HUVEC. In a ddition, cases with a high IL-8 level in cancerous tissue had a significant ly higher frequency of portal vein invasion, venous invasion and bile duct invasion (p<0.05). In the cultures of 7 HCC cell lines IL-8 secretion into culture medium increased with the treatment of IL-1<beta> or tumor necrosis factor-alpha. This showed IL-8 expression is regulated by inflammatory cyt okines. IL-8 produced by HCC is an angiogenesis factor of HCC, but it could have a much more important role in the invasion and metastasis of HCC.