RRC ID |
44656
|
著者 |
Ishino R, Minami K, Tanaka S, Nagai M, Matsui K, Hasegawa N, Roeder RG, Asano S, Ito M.
|
タイトル |
FGF7 supports hematopoietic stem and progenitor cells and niche-dependent myeloblastoma cells via autocrine action on bone marrow stromal cells in vitro.
|
ジャーナル |
Biochem Biophys Res Commun
|
Abstract |
FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1(+/+) MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1(-/-) MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1(+/+) and Med1(-/-) MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells.
|
巻・号 |
440(1)
|
ページ |
125-31
|
公開日 |
2013-10-11
|
DOI |
10.1016/j.bbrc.2013.09.044
|
PII |
S0006-291X(13)01515-5
|
PMID |
24051090
|
MeSH |
Animals
Cell Line
Cell Line, Tumor
Cell Proliferation
Cells, Cultured
Fibroblast Growth Factor 7 / genetics
Fibroblast Growth Factor 7 / metabolism*
Gene Deletion
Gene Expression Regulation*
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / metabolism*
Humans
Leukemia / genetics
Leukemia / metabolism*
Mediator Complex Subunit 1 / genetics
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / metabolism*
Mice
Mice, Inbred C57BL
Receptor, Fibroblast Growth Factor, Type 2 / genetics
Receptor, Fibroblast Growth Factor, Type 2 / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Signal Transduction
|
IF |
2.985
|
引用数 |
9
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
OP9(RCB1124) |