Expression of leukemia-inhibitory factor as an autocrinal growth factor inhuman medulloblastomas

Medulloblastoma is the most frequent pediatric brain tumor, with the capaci ties of rapid proliferation and intracranal dissemination. However, the fac tor(s) regulating medulloblastoma growth has not yet been well characterize d. Leukemia-inhibitory factor (LIF) and interleukin-6 (IL-6) play different roles in the formation/progression of various embryonic and pediatric tumo rs, but their biological effects on medulloblastoma cells are less well kno wn. Therefore, in vivo and in vitro expression of LIF, IL-6 and their signa l 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 sample s 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 m edulloblastoma cells. The growth of Med-3 cells was efficiently inhibited e ither by anti-LIF antibody or by antisense LIF oligonucleotide. Addition of exogenous human recombinant IL-6 could dramatically enhance Med-3 cell out growth. 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: prolif eration of medulloblastoma cells.