Expression of leukemia-inhibitory factor as an autocrinal growth factor in human medulloblastomas

Medulloblastoma is the most frequent pediatric brain tumor, with the capacities of rapid proliferation and intracranial dissemination. However, the factor(s) regulating medulloblastoma growth has not yet been well characterized. Leukemia-inhibitory factor (LIF) and interleukin-6 (IL-6) play different roles in the formation/progression of various embryonic and pediatric tumors, but their biological effects on medulloblastoma cells are less well known. Therefore, in vivo and in vitro expression of LIF, IL-6 and their signal transducer genes encoding LIF receptor (LIFR), IL-6 receptor (IL-6R) and gp130 in human medulloblastoma cells were investigated by multiple cellular and molecular biology approaches. The results revealed that LIF expression could be found in 26 out of 28 tumors/cell line and over 90% of the samples expressed LIFR, IL-6R and gp130. In contrast, none of the samples showed IL-6 expression. An established medulloblastoma cell line, Med-3, was used to evaluate the potential effects of LIF and IL-6 on the proliferation of medulloblastoma cells. The growth of Med-3 cells was efficiently inhibited either by anti-LIF antibody or by antisense LIF oligonucleotide. Addition of exogenous human recombinant IL-6 could dramatically enhance Med-3 cell outgrowth. Our data thus for the first time demonstrated the important role of LIF as an autocrinal and IL-6 as a paracrinal growth factor in the proliferation of medulloblastoma cells.