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Tinhofer, I; Marschitz, I; Henn, T; Egle, A; Greil, R.
Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma.
Blood. 2000; 95(2):610-618 Doi: 10.1182/blood.V95.2.610 [OPEN ACCESS]
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Co-authors Med Uni Graz: Marschitz Ingrid Christine
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Abstract:: Interleukin-15 (IL-15) induces proliferation and promotes cell survival of human T and B lymphocytes, natural killer cells, and neutrophils. Here we report the constitutive expression of a functional IL-15 receptor (IL-15R) in 6 of 6 myeloma cell lines and in CD38(high)/CD45(low )plasma cells belonging to 14 of 14 patients with multiple myeloma. Furthermore, we detected IL-15 transcripts in all 6 myeloma cell lines, and IL-15 protein in 4/6 cell lines and also in the primary plasma cells of 8/14 multiple myeloma patients. Our observations confirm the existence of an autocrine IL-15 loop and point to the potential paracrine stimulation of myeloma cells by IL-15 released from the cellular microenvironment. Blocking autocrine IL-15 in cell lines increased the rate of spontaneous apoptosis, and the degree of this effect was comparable to the pro-apoptotic effect of depleting autocrine IL-6 by antibody targeting. IL-15 was also capable of substituting for autocrine IL-6 in order to promote cell survival and vice versa. In short-term cultures of primary myeloma cells, the addition of IL-15 reduced the percentage of tumor cells spontaneously undergoing apoptosis. Furthermore, IL-15 lowered the responsiveness to Fas-induced apoptosis and to cytotoxic treatment with vincristine and doxorubicin but not with dexamethasone. These data add IL-15 to the list of important factors promoting survival of multiple myeloma cells and demonstrate that it can be produced and be functionally active in an autocrine manner. (Blood. 2000;95:610-618)
Find related publications in this database (using NLM MeSH Indexing): Adult -; Aged -; Antigens, CD95 - analysis; Apoptosis - drug effects; Bone Marrow Cells - immunology; Flow Cytometry - immunology; Hematopoietic Stem Cells - drug effects; Humans - drug effects; Interleukin-15 - analysis; Leukocytes, Mononuclear - immunology; Membrane Glycoproteins - analysis; Middle Aged - analysis; Multiple Myeloma - immunology; Plasma Cells - immunology; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins c-bcl-2 - analysis; Receptors, Interleukin-2 - analysis; Reverse Transcriptase Polymerase Chain Reaction - analysis; Transcription, Genetic - analysis; Tumor Cells, Cultured - analysis; bcl-2-Associated X Protein - analysis