title: Fibroblast nemosis arrests growth and induces differentiation of human leukemia cells.
abstract: Interactive signaling between cancer cells and stroma plays an important role in determining tumor development. We recently found tumor cell-derived factors to induce fibroblast clustering, and that the high amounts of hepatocyte growth factor/scatter factor (HGF/SF) produced by these cell-cell contact-activated fibroblasts enhanced the invasiveness of c-Met-expressing cancer cells. We now observed that leukemia cells lacking c-Met respond to this novel type of fibroblast activation, nemosis, with growth arrest and differentiation to a dendritic cell-like phenotype. This effect was counteracted by introduction of c-Met expression into these cells. Moreover, those leukemia cell lines harboring properly processed c-Met showed no effect in response to nemosis. We propose this effect to be mediated by nemosis-derived cytokine signals, and present the potential candidates induced in the nemotic fibroblasts: interleukins-1, -6, -8, -11, leukemia inhibitory factor and granulocyte-macrophage-colony-stimulating factor. Our results emphasize the role of activated stromal fibroblasts in controlling progression of certain hematologic malignancies in a c-Met expression-dependent manner.
authors.affiliation: Institute of Biomedicine, Pharmacology, University of Helsinki, Finland. esko.kankuri@helsinki.fi
authors.forename: Esko
authors.initials: E
authors.lastname: Kankuri
authors.forename: Olga
authors.initials: O
authors.lastname: Babusikova
authors.forename: Kristina
authors.initials: K
authors.lastname: Hlubinova
authors.forename: Pertteli
authors.initials: P
authors.lastname: Salmenperä
authors.forename: Carla
authors.initials: C
authors.lastname: Boccaccio
authors.forename: Werner
authors.initials: W
authors.lastname: Lubitz
authors.forename: Ari
authors.initials: A
authors.lastname: Harjula
authors.forename: Jozef
authors.initials: J
authors.lastname: Bizik
mesh_terms: D000954:Antigens, Surface / Q000276:immunology; D017209:Apoptosis; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D019859:Proto-Oncogene Proteins c-met