Abstract
Stromal cell-derived factor (SDF)-1α mediates migration of normal hematopoietic stem cells, but its role in hematological malignancies is undefined. In this study, we detected SDF-1α in bone marrow (BM) plasma from 10 patients with MM (multiple myeloma; 2.6 ± 1.5 ng/ml) and BM stromal cell culture supernatants from 5 patients with MM (0.6 ± 0.2 ng/ ml). We show that SDF-1α promotes proliferation, induces migration, and protects against dexamethasone-induced apoptosis in MM cells, but these effects are only modest. In MM cell lines and patient MM cells, SDF-1α induces phosphorylation of p42/44 mitogen-activated protein kinase, as well as Akt and its downstream target Bad, and also activates nuclear factor-κB. In the BM milieu, SDF-1α upregulates secretion of interleukin 6 and vascular endothelial growth factor in BM stromal cells, which promote tumor cell growth, survival, and migration. These data demonstrate that SDF-1α promotes growth, migration and drug resistance of MM cells in the BM microenvironment, but these effects are only modest, SDF-1α therefore does not represent a target for novel therapeutics in this disease.
Original language | English |
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Pages (from-to) | 539-544 |
Number of pages | 6 |
Journal | Molecular Cancer Therapeutics |
Volume | 1 |
Issue number | 7 |
Publication status | Published - May 2002 |
Externally published | Yes |
Keywords
- Apoptosis
- Blotting, Western
- Bone Marrow/metabolism
- Bone Marrow Cells/metabolism
- Carrier Proteins/metabolism
- Cell Division
- Cell Movement
- Cells, Cultured
- Chemokine CXCL12
- Chemokines, CXC/metabolism
- DNA/biosynthesis
- Dexamethasone/pharmacology
- Dose-Response Relationship, Drug
- Endothelial Growth Factors/metabolism
- Flow Cytometry
- Humans
- Intercellular Signaling Peptides and Proteins/metabolism
- Interleukin-6/metabolism
- Lymphokines/metabolism
- Multiple Myeloma/metabolism
- NF-kappa B/metabolism
- Phosphorylation
- Signal Transduction
- Time Factors
- Up-Regulation
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- bcl-Associated Death Protein
ASJC Scopus subject areas
- Oncology
- Cancer Research