C/EBP alpha Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity
| Autor: | Eric M. Kallin, Jose A. Richter-Larrea, Thomas Graf, Jose A. Martinez-Climent, Eloy F. Robles, Francesca Rapino |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Lymphoma
B-Cell Antineoplastic Agents Hormonal Transplantation Heterologous Cell 030204 cardiovascular system & hematology Biology General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Phagocytosis Cell Line Tumor CCAAT-Enhancer-Binding Protein-alpha medicine Animals Humans Macrophage Cell Lineage lcsh:QH301-705.5 B cell 030304 developmental biology 0303 health sciences Leukemia Macrophages Transdifferentiation medicine.disease Virology Molecular biology 3. Good health Tamoxifen medicine.anatomical_structure lcsh:Biology (General) Cell culture 030220 oncology & carcinogenesis Cell Transdifferentiation Transcriptome Reprogramming |
| Zdroj: | Cell Reports; Vol 3 Cell Reports, Vol 3, Iss 4, Pp 1153-1163 (2013) Cell Reports, Vol 19, Iss 6, p 1281 (2017) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2013.03.003 |
| Popis: | SummaryEarlier work demonstrated that the transcription factor C/EBPα can convert immature and mature murine B lineage cells into functional macrophages. Testing >20 human lymphoma and leukemia B cell lines, we found that most can be transdifferentiated at least partially into macrophage-like cells, provided that C/EBPα is expressed at sufficiently high levels. A tamoxifen-inducible subclone of the Seraphina Burkitt lymphoma line, expressing C/EBPαER, could be efficiently converted into phagocytic and quiescent cells with a transcriptome resembling normal macrophages. The converted cells retained their phenotype even when C/EBPα was inactivated, a hallmark of cell reprogramming. Interestingly, C/EBPα induction also impaired the cells’ tumorigenicity. Likewise, C/EBPα efficiently converted a lymphoblastic leukemia B cell line into macrophage-like cells, again dramatically impairing their tumorigenicity. Our experiments show that human cancer cells can be induced by C/EBPα to transdifferentiate into seemingly normal cells at high frequencies and provide a proof of principle for a potential new therapeutic strategy for treating B cell malignancies. |
| Databáze: | OpenAIRE |
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