IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells
| Autor: | Ho Yeon Chung, Natalie S. Callander, G. David Roodman, Lori A. Ehrlich, Jun Won Lee, Sun Jin Choi, Diane F. Jelinek |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Myeloid Immunology Down-Regulation Osteoclasts Bone Marrow Cells Transfection Biochemistry Bone resorption Antibodies Osteoclast hemic and lymphatic diseases Internal medicine Cell Line Tumor Proto-Oncogene Proteins medicine Humans RNA Messenger Bone Resorption Chemokine CCL4 Multiple myeloma Regulation of gene expression Membrane Glycoproteins biology Receptor Activator of Nuclear Factor-kappa B RANK Ligand Cell Differentiation Cell Biology Hematology Macrophage Inflammatory Proteins medicine.disease DNA-Binding Proteins Gene Expression Regulation Neoplastic Haematopoiesis medicine.anatomical_structure Endocrinology RANKL Core Binding Factor Alpha 2 Subunit Cancer research biology.protein Interleukin-3 Bone marrow Carrier Proteins Multiple Myeloma Cell Division Transcription Factors |
| Zdroj: | Blood. 103(6) |
| ISSN: | 0006-4971 |
| Popis: | Macrophage inflammatory protein–1α (MIP-1α) gene expression is abnormally regulated in multiple myeloma (MM) owing to imbalanced expression of the acute myeloid leukemia–1A (AML-1A) and AML-1B transcription factors. We hypothesized that the increased expression ratios of AML-1A to AML-1B also induced abnormal expression of other hematopoietic and bone-specific genes that contribute to the poor prognosis of MM patients with high levels of MIP-1α. We found that interleukin-3 (IL-3) was also induced by the imbalanced AML-1A and AML-1B expression in myeloma. IL-3 mRNA levels were increased in CD138+ purified myeloma cells with increased AML-1A–to–AML-1B expression from MM patients, and IL-3 protein levels were significantly increased in freshly isolated bone marrow plasma from MM patients (66.4 ± 12 versus 22.1 ± 8.2 pg/mL; P = .038). IL-3 in combination with MIP-1α or receptor activator of nuclear factor–kappa B ligand (RANKL) significantly enhanced human osteoclast (OCL) formation and bone resorption compared with MIP-1α or RANKL alone. IL-3 stimulated the growth of interleukin-6 (IL-6)–dependent and IL-6–independent myeloma cells in the absence of IL-6, even though IL-3 did not induce IL-6 expression by myeloma cells. These data suggest that increased IL-3 levels in the bone marrow microenvironment of MM patients with imbalanced AML-1A and AML-1B expression can increase bone destruction and tumor cell growth. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|