Hepatocyte growth factor promotes migration of human myeloma cells.
Multiple myeloma is characterized by the accumulation and dissemination of malignant plasma cells in the bone marrow. Cell migration is thought to be important for these events. We studied migration in a Transwell two-chamber assay and tested the motogenic effect of various cytokines. In addition to insulin-like growth factor-1 and stromal cell-derived growth factor-1alpha, previously known as chemoattractants for myeloma cells, we identified hepatocyte growth factor as a potent attractant for myeloma cells. Hepatocyte growth factor-mediated migration was dependent on phosphatidylinositol-3-kinase, involved the MAPK/Erk signaling cascade and VLA-4 integrins, but did not involve Akt, mTOR or G proteins.
Holt
Randi Utne
RU
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, MTFS, N-7489 Trondheim, Norway. randi.u.holt@ntnu.no
Fagerli
Unn-Merete
UM
Baykov
Vadim
V
Rø
Torstein Baade
TB
Hov
Håkon
H
Waage
Anders
A
Sundan
Anders
A
Børset
Magne
M
D001853:Bone Marrow / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology; D054377:Chemokine CXCL12 / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000032:analysis; D017228:Hepatocyte Growth Factor / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D039041:Integrin alpha4beta1 / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009101:Multiple Myeloma / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010950:Plasma Cells / Q000187:drug effects* / Q000473:pathology; D011494:Protein Kinases / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D054377:Chemokine CXCL12; D016207:Cytokines; D004791:Enzyme Inhibitors; D019204:GTP-Binding Proteins; D017228:Hepatocyte Growth Factor; D007211:Indoles; D039041:Integrin alpha4beta1; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D019859:Proto-Oncogene Proteins c-met; D011994:Recombinant Proteins; D013450:Sulfones; D058570:TOR Serine-Threonine Kinases; C480541:5-((2,6-dichlorobenzyl)sulfonyl)-3-((3,5-dimethyl-4-((2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-1,3-dihydro-2H-indol-2-one; C515255:CXCL12 protein, human; C066855:HGF protein, human; C546842:MTOR protein, human