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Multiple myeloma cells adapted to long-exposure of hypoxia exhibit stem cell characters with TGF-β/Smad pathway activation
- Source :
- Biochemical and biophysical research communications. 496(2)
- Publication Year :
- 2017
-
Abstract
- The emergence of new molecular targeting agents has improved the prognosis of patients with multiple myeloma (MM). However, MM remains incurable because MM stem cells are likely resistant to these agents. Thus, it is important to further investigate the biology of MM stem cells, which reside in the hypoxic bone marrow niche. In this study, we established and investigated the characteristics of hypoxia-adapted MM (HA-MM) cells, which could proliferate for more than six months under hypoxic conditions (1% O2). The G0 fraction of HA-MM cells was larger than that of parental MM cells under normoxic conditions (20% O2). HA-MM cells possess enhanced tumorigenicity in primary and secondary transplantation studies. HA-MM cells also exhibited increased mRNA levels of stem cell markers and an enhanced self-renewal ability, and thus demonstrated characteristics of MM stem cells. These cells overexpressed phosphorylated Smad2, and treatment with a transforming growth factor (TGF)-β/Smad signaling inhibitor decreased their clonogenicity in a replating assay. In conclusion, MM cells adapted to long-exposure of hypoxia exhibit stem cell characters with TGF-β/Smad pathway activation.
- Subjects :
- 0301 basic medicine
Biophysics
SMAD
Smad2 Protein
Stem cell marker
Biochemistry
Immunophenotyping
03 medical and health sciences
Mice
0302 clinical medicine
Mice, Inbred NOD
Transforming Growth Factor beta
Cell Line, Tumor
medicine
Biomarkers, Tumor
Animals
Humans
Molecular Biology
Multiple myeloma
Cell Line, Transformed
Chemistry
SOXB1 Transcription Factors
Stem Cells
Cell Biology
Nanog Homeobox Protein
Hypoxia (medical)
medicine.disease
Survival Analysis
Cell Hypoxia
Transplantation
Gene Expression Regulation, Neoplastic
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
Female
Bone marrow
medicine.symptom
Stem cell
Multiple Myeloma
Octamer Transcription Factor-3
Neoplasm Transplantation
Transforming growth factor
Signal Transduction
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 496
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....fa40adba980f5b9622dc4c69dd1efb3b