Back to Search
Start Over
Growth differentiating factor 15 enhances the tumor-initiating and self-renewal potential of multiple myeloma cells.
- Source :
-
Blood [Blood] 2014 Jan 30; Vol. 123 (5), pp. 725-33. Date of Electronic Publication: 2013 Dec 17. - Publication Year :
- 2014
-
Abstract
- Disease relapse remains a major factor limiting the survival of cancer patients. In the plasma cell malignancy multiple myeloma (MM), nearly all patients ultimately succumb to disease relapse and progression despite new therapies that have improved remission rates. Tumor regrowth indicates that clonogenic growth potential is continually maintained, but the determinants of self-renewal in MM are not well understood. Normal stem cells are regulated by extrinsic niche factors, and the tumor microenvironment (TME) may similarly influence tumor cell clonogenic growth and self-renewal. Growth differentiation factor 15 (GDF15) is aberrantly secreted by bone marrow stromal cells (BMSCs) in MM. We found that GDF15 is produced by BMSCs after direct contact with plasma cells and enhances the tumor-initiating potential and self-renewal of MM cells in a protein kinase B- and SRY (sex-determining region Y)-box-dependent manner. Moreover, GDF15 induces the expansion of MM tumor-initiating cells (TICs), and changes in the serum levels of GDF15 were associated with changes in the frequency of clonogenic MM cells and the progression-free survival of MM patients. These findings demonstrate that GDF15 plays a critical role in mediating the interaction among mature tumor cells, the TME, and TICs, and strategies targeting GDF15 may affect long-term clinical outcomes in MM.
- Subjects :
- Animals
Cell Line, Tumor
Cell Proliferation
Growth Differentiation Factor 15 blood
Humans
Mice
Mice, Inbred C57BL
Multiple Myeloma blood
Multiple Myeloma pathology
Proto-Oncogene Proteins c-akt metabolism
SOXB1 Transcription Factors metabolism
Signal Transduction
Growth Differentiation Factor 15 metabolism
Multiple Myeloma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 123
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 24345755
- Full Text :
- https://doi.org/10.1182/blood-2013-08-524025