Interleukin-15 blocks apoptosis and induces proliferation of the human myeloma cell line OH-2 and freshly isolated myeloma cells.
The growth factor-dependent myeloma cell line OH-2, which has previously been shown to be responsive to interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and lymphotoxin, was examined for response to other growth factors. Enhanced proliferation was found in the presence of IL-10, IL-15, IL-2 and insulin growth factor (IGF)-1. Proliferation was strongest in response to IL-6, intermediate and roughly equipotent in response to IL-15, IL-10 and TNF-alpha, and modest in response to IL-2 and IGF-1. IL-15 was synergistic with TNF-alpha, whereas combinations of IL-15 and the other cytokines were merely additive. IL-15-induced proliferation could not be blocked by neutralizing antibody against gp 130, the common transducer chain of IL-6 and related cytokines. IL-15 and IL-6 prevented apoptosis equally well, both better than TNF-alpha, IL-10, and IGF-1. In four out of six samples of purified primary cells, IL-15 and IL-6 induced proliferation. Furthermore, IL-15 mRNA was detected by RT-PCR in most myeloma cell lines and freshly isolated purified patient samples. IL-15 protein was detectable only in one out of about 20 tested cell supernatants from patients and myeloma cell lines. The OH-2 cell line is multi-responsive to cytokines and is a good system for the study of integration of cytokine signal transduction and growth control in myeloma. IL-15 represents a novel modality of growth regulation in myeloma.
Hjorth-Hansen
H
H
Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology (NTNU), Trondheim. henrikhh@medisin.ntnu.no
Waage
A
A
Börset
M
M
D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019409:Interleukin-15; D012333:RNA, Messenger