Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma
| Autor: | Inge Tinhofer, Traudl Henn, Alexander Egle, Ingrid Marschitz, Richard Greil |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Fas Ligand Protein Transcription Genetic medicine.medical_treatment Immunology Plasma Cells Apoptosis Bone Marrow Cells Biology Biochemistry Paracrine signalling Proto-Oncogene Proteins medicine Tumor Cells Cultured Cytotoxic T cell Humans fas Receptor Autocrine signalling Multiple myeloma Aged bcl-2-Associated X Protein Interleukin-15 Membrane Glycoproteins Receptors Interleukin-15 Reverse Transcriptase Polymerase Chain Reaction Receptors Interleukin-2 Cell Biology Hematology Middle Aged medicine.disease Flow Cytometry Hematopoietic Stem Cells Interleukin-15 receptor Cytokine Proto-Oncogene Proteins c-bcl-2 Cell culture Interleukin 15 Cancer research Leukocytes Mononuclear Multiple Myeloma |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0006-4971 |
| Popis: | 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) |
| Databáze: | OpenAIRE |
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