Hepatocyte growth factor induces hypoxia-related interleukin-8 expression in lung adenocarcinoma cells.

Rapid growth of cancer cells often creates insufficient supply of oxygen and nutrients in the tumour nest. The frequent detection of hypoxia-inducible factor (HIF) and interleukin-8 (IL-8) in afflicted tissues suggests that IL-8 expression could be associated with elevated levels of HIF. Recently, we found that hypoxia also upregulated the expression of hepatocyte growth factor (HGF) in lung adenocarcinoma (LAD) cells. However, the relationship between HGF and IL-8 has not been investigated in LAD cells. In this study, we found that HGF induced IL-8 expression in LAD. Interestingly, hypoxia also increased the level of prostaglandin F(2alpha) (PGF(2alpha)), a product of dihydrodiol dehydrogenase (DDH). When expression of DDH was suppressed by siRNA, the levels of PGF(2alpha), HGF and IL-8 were reduced; however, their levels returned to normal after DDH was reintroduced. These data suggest that hypoxia induces biosynthesis of PGF(2alpha), which then activates HGF and IL-8 expression. The results provide a reasonable explanation of how PGF(2alpha), HGF and IL-8 exert their effects on cancer cell metastasis.