Interleukin-6 inhibits the chemotaxis of human malignant plasma cell lines.
The chemotaxis of human malignant plasma cells is promoted by two extracellular matrix proteins (ECMs): fibronectin (FN) and laminin (LN). We examined the effect of the supernatant from a bone marrow stroma cell line, KM-101, on the chemotaxis of human malignant plasma cell lines to assess the chemotaxis-regulatory roles of the bone marrow microenvironment. Five human malignant plasma cell lines, FR4ds, OPM-1ds, U266/B1, RPMI-8226 and ARH-77 showed different profiles of the expression of beta 1 integrins of FN and LN receptors. FR4ds, OPM-1ds and U266/B1 cells showed chemotaxis promoted by FN (ChFN) and LN (ChLN). ARH-77 cells showed ChFN but not ChLN. RPMI-8226 cells did not show either ChFN or ChLN. The supernatant from KM-101 cells inhibited the chemotaxis of each of these cell lines regardless of whether the chemotaxis was promoted by FN or LN. Among the cytokines produced by KM-101 cells, it was postulated that IL-6 mediated this inhibitory effect because anti-IL-6 monoclonal antibody (MoAb) and anti-IL-6 receptor MoAb significantly reversed the inhibition. Recombinant IL-6 (rIL-6) also exhibited a similar inhibitory effect. Because anti-gp130 MoAb significantly reversed the chemotaxis inhibitory effect of rIL-6, the inhibitory signal is probably transduced via the signal transducing receptor component, gp130. The chemotaxis-regulatory effect is another previously unrecognized function of this pleiotropic cytokine, IL-6. High levels of IL-6 in the bone marrow microenvironment of patients with multiple myeloma appears to be favourable for the localization of myeloma cells there.
Shibayama
H
H
Department of Haematology and Oncology, Osaka University Medical School, Japan.
Tagawa
S
S
Hattori
H
H
Harigaya
K
K
Taga
T
T
Machii
T
T
Kitani
T
T
D015703:Antigens, CD / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D007952:Leukemia, Plasma Cell / Q000378:metabolism / Q000473:pathology*; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D010954:Plasmacytoma / Q000378:metabolism / Q000473:pathology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D019947:Receptors, Interleukin-6; D017474:Receptors, Laminin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000093242:Interleukin-6 Inhibitors
D015703:Antigens, CD; D015850:Interleukin-6; D016186:Receptor, Macrophage Colony-Stimulating Factor; D017469:Receptors, Fibronectin; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D017474:Receptors, Laminin; D000093242:Interleukin-6 Inhibitors