The gp 130 family cytokines IL-6, LIF and OSM but not IL-11 can reverse the anti-proliferative effect of dexamethasone on human myeloma cells.
In order to understand the mechanisms supporting steroid escape in patients with multiple myeloma (MM), three IL-6 autocrine human myeloma cell lines, LP1, OPM2 and L363, have been treated with dexamethasone in the presence or absence of cytokines belonging to the gp 130 family: IL-6, LIF, OSM and IL-11. With pharmacological doses of dexamethasone, a dramatic growth arrest was observed in all the cell lines. IL-6 completely reversed this inhibition. Of note, this IL-6 induced reversion was still seen with very low amounts of IL-6 (12 pg/ml). Finally, whereas LIF and OSM had clear growth-promoting effects on OPM2 only, both cytokines (but not IL-11) reversed the dexamethasone-induced growth arrest in all the cell lines. Therefore the high levels of IL-6 (ng/ml) observed in the MM intermediate milieu and the putative presence of LIF and OSM can easily counteract the effects of dexamethasone in vivo.
Juge-Morineau
N
N
Laboratoire d'Oncogénèse Immunohématologique, Inserm U211, Nantes, France.
François
S
S
Puthier
D
D
Godard
A
A
Bataille
R
R
Amiot
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000473:pathology*; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M; D003907:Dexamethasone