Blood, 2011-04, Vol.117 (17), p.4409-4419
2011
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Details
- Autor(en) / Beteiligte
- Titel
- Lenalidomide targets clonogenic side population in multiple myeloma: pathophysiologic and clinical implications
- Ist Teil von
- Blood, 2011-04, Vol.117 (17), p.4409-4419
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2011
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Recurrence of multiple myeloma (MM) after therapy suggests the presence of tumor-initiating subpopulations. In our study, we performed flow cytometry–based Hoechst 33342 staining to evaluate the existence of a MM population with stem-like features known as side population (SP) cells. SP cells exhibit substantial heterogeneity in MM cell lines and primary MM cells; express CD138 antigen in MM cell lines; display higher mRNA expression and functional activity of ABCG2 transporter; and have a higher proliferation index compared with non-SP cells. We observed evidence for clonogenic potential of SP cells, as well as the ability of SP cells to regenerate original population. Moreover, SP cells revealed higher tumorigenicity compared with non-SP cells. Importantly, lenalidomide decreased the percentage and clonogenicity of SP cells, and also induced phosphorylation changes in Akt, GSK-3α/β, MEK1, c-Jun, p53, and p70S6K in SP cells. Adherence to bone marrow stromal cells (BMSCs) increased the percentage, viability, and proliferation potential of SP cells. Lenalidomide and thalidomide abrogated this stimulatory effect of BMSCs and significantly decreased the percentage of SP cells. Our studies demonstrate a novel mechanism of action for lenalidomide, namely targeting SP fraction, providing the framework for new therapeutic strategies targeting subpopulations of MM cells including presumptive stem cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-4971eISSN: 1528-0020DOI: 10.1182/blood-2010-02-267344Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3099565
- Format
- –
- Schlagworte
- Angiogenesis Inhibitors - pharmacology, Antineoplastic Agents - pharmacology, ATP-Binding Cassette Transporters - genetics, Bone Marrow Cells - cytology, Bone Marrow Cells - drug effects, Bone Marrow Cells - physiology, Cell Division - drug effects, Cell Fractionation, Cell Line, Tumor, Cell Survival - drug effects, Colony-Forming Units Assay, Drug Resistance, Neoplasm, Humans, Lenalidomide, Lymphoid Neoplasia, Multiple Myeloma - drug therapy, Multiple Myeloma - pathology, Multiple Myeloma - physiopathology, Neoplasm Recurrence, Local - prevention & control, Neoplastic Stem Cells - drug effects, Neoplastic Stem Cells - pathology, Plenary Paper, Signal Transduction - drug effects, Stromal Cells - cytology, Stromal Cells - drug effects, Stromal Cells - physiology, Syndecan-1 - metabolism, Thalidomide - analogs & derivatives, Thalidomide - pharmacology