Signaling through interleukin-6 receptor supports blast cell proliferation in acute myeloblastic leukemia.
The role of the interleukin-6/interleukin-6 receptor (IL-6/IL-6R) system in regulating blast cell growth in 8 acute myeloblastic leukemia (AML) patient-derived cell lines was investigated. As they all expressed IL-6R and as none of them responded to exogenous IL-6 under conventional serum-supplemented culture conditions, we investigated whether signaling through IL-6R plays any role in maintaining their spontaneous colony growth. This was done by treating the cells with monoclonal antibodies made against the ligand-specific IL-6R alpha-chain or the signal transducer gp130. In serum-supplemented cultures inhibition of gp130 function did not affect the cell line growth, whereas anti-IL-6R alpha-chain antibody reduced colony growth. While some of the cell lines also showed similar growth characteristics in a serum-free environment, some others changed their growth pattern and stopped responding to anti-IL-6R alpha-chain treatment. At the same time, these cell lines also began to respond to exogenously added IL-6 and, interestingly, were stimulated by anti-gp130 antibody. Hence, in some of the blast cells, clonogenic cell growth seemed to be also negatively controlled by an endogenously produced growth-depressing cytokine or cytokines that utilize gp130. All the cell lines, whether cultured in the presence or absence of serum expressed IL-6 both at mRNA and protein level. The current results indicate that AML cells can use IL-6 as a growth stimulating factor, supplied either paracrinely or autocrinely. This could implicate the use of anti-IL-6R alpha-chain antagonists in AML treatment, not IL-6.
Säily
M
M
Department of Internal Medicine, University of Oulu, Finland.
Koistinen
P
P
Zheng
A
A
Savolainen
E R
ER
D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology*; D019947:Receptors, Interleukin-6 / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D019947:Receptors, Interleukin-6