C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity
Earlier 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, pr...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2013-04-01
|
Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713001101 |
id |
doaj-ebef9f95d9b541daab913c4c1d5ee4cf |
---|---|
record_format |
Article |
spelling |
doaj-ebef9f95d9b541daab913c4c1d5ee4cf2020-11-25T00:19:35ZengElsevierCell Reports2211-12472013-04-01341153116310.1016/j.celrep.2013.03.003C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their TumorigenicityFrancesca Rapino0Eloy F. Robles1Jose A. Richter-Larrea2Eric M. Kallin3Jose A. Martinez-Climent4Thomas Graf5Center for Genomic Regulation, Universidad Pompeu Fabra and Institució Catalana de Recerca i Estudis Avançats, Dr. Aiguader 88, 08003 Barcelona, SpainCenter for Applied Medical Research, University of Navarra, Pio XII 55 31008 Pamplona, SpainCenter for Applied Medical Research, University of Navarra, Pio XII 55 31008 Pamplona, SpainCenter for Genomic Regulation, Universidad Pompeu Fabra and Institució Catalana de Recerca i Estudis Avançats, Dr. Aiguader 88, 08003 Barcelona, SpainCenter for Applied Medical Research, University of Navarra, Pio XII 55 31008 Pamplona, SpainCenter for Genomic Regulation, Universidad Pompeu Fabra and Institució Catalana de Recerca i Estudis Avançats, Dr. Aiguader 88, 08003 Barcelona, Spain Earlier 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. http://www.sciencedirect.com/science/article/pii/S2211124713001101 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Francesca Rapino Eloy F. Robles Jose A. Richter-Larrea Eric M. Kallin Jose A. Martinez-Climent Thomas Graf |
spellingShingle |
Francesca Rapino Eloy F. Robles Jose A. Richter-Larrea Eric M. Kallin Jose A. Martinez-Climent Thomas Graf C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity Cell Reports |
author_facet |
Francesca Rapino Eloy F. Robles Jose A. Richter-Larrea Eric M. Kallin Jose A. Martinez-Climent Thomas Graf |
author_sort |
Francesca Rapino |
title |
C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity |
title_short |
C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity |
title_full |
C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity |
title_fullStr |
C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity |
title_full_unstemmed |
C/EBPα Induces Highly Efficient Macrophage Transdifferentiation of B Lymphoma and Leukemia Cell Lines and Impairs Their Tumorigenicity |
title_sort |
c/ebpα induces highly efficient macrophage transdifferentiation of b lymphoma and leukemia cell lines and impairs their tumorigenicity |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2013-04-01 |
description |
Earlier 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.
|
url |
http://www.sciencedirect.com/science/article/pii/S2211124713001101 |
work_keys_str_mv |
AT francescarapino cebpainduceshighlyefficientmacrophagetransdifferentiationofblymphomaandleukemiacelllinesandimpairstheirtumorigenicity AT eloyfrobles cebpainduceshighlyefficientmacrophagetransdifferentiationofblymphomaandleukemiacelllinesandimpairstheirtumorigenicity AT josearichterlarrea cebpainduceshighlyefficientmacrophagetransdifferentiationofblymphomaandleukemiacelllinesandimpairstheirtumorigenicity AT ericmkallin cebpainduceshighlyefficientmacrophagetransdifferentiationofblymphomaandleukemiacelllinesandimpairstheirtumorigenicity AT joseamartinezcliment cebpainduceshighlyefficientmacrophagetransdifferentiationofblymphomaandleukemiacelllinesandimpairstheirtumorigenicity AT thomasgraf cebpainduceshighlyefficientmacrophagetransdifferentiationofblymphomaandleukemiacelllinesandimpairstheirtumorigenicity |
_version_ |
1725371141660344320 |