title: Expression of leukemia-inhibitory factor as an autocrinal growth factor in human medulloblastomas.
abstract: 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.
authors.affiliation: Division of Molecular Biology, Shenyang Medical College, P.R. China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: J W
authors.initials: JW
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Gang
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.forename: H
authors.initials: H
authors.lastname: Li
mesh_terms: D015139:Blotting, Southern; D015153:Blotting, Western; D002528:Cerebellar Neoplasms / Q000737:chemistry / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006131:Growth Inhibitors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008527:Medulloblastoma / Q000737:chemistry / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D012334:RNA, Neoplasm