Fibroblast nemosis arrests growth and induces differentiation of human leukemia cells.
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.
Kankuri
Esko
E
Institute of Biomedicine, Pharmacology, University of Helsinki, Finland. esko.kankuri@helsinki.fi
Babusikova
Olga
O
Hlubinova
Kristina
K
Salmenperä
Pertteli
P
Boccaccio
Carla
C
Lubitz
Werner
W
Harjula
Ari
A
Bizik
Jozef
J
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
D000954:Antigens, Surface; D016207:Cytokines; D019859:Proto-Oncogene Proteins c-met