RRC ID |
45385
|
著者 |
Miyatake Y, Sheehy N, Ikeshita S, Hall WW, Kasahara M.
|
タイトル |
Anchorage-dependent multicellular aggregate formation induces CD44 high cancer stem cell-like ATL cells in an NF-κB- and vimentin-dependent manner.
|
ジャーナル |
Cancer Lett
|
Abstract |
Adult T-cell leukemia/lymphoma (ATL) is an intractable T-cell malignancy accompanied by massive invasion of lymphoma cells into various tissues. We demonstrate here that ATL cells cultured on a layer of epithelial-like feeder cells form anchorage-dependent multicellular aggregates (Ad-MCAs) and that a fraction of MCA-forming ATL cells acquire CD44 high cancer stem cell-like phenotypes. ATL cells forming Ad-MCAs displayed extracellular microvesicles with enhanced expression of CD44v9 at cell synapses, augmented expression of multidrug resistance protein 1, and increased NF-κB activity. Blockade of the NF-κB pathway dramatically reduced Ad-MCA formation by ATL cells and the emergence of CD44 high ATL cells, but left a considerable number of ATL cells adhering to the feeder layer. Disruption of vimentin cytoskeleton by treatment with withaferin A, a natural steroidal lactone, suppressed not only the adhesion of ATL cells to the feeder layer but also subsequent Ad-MCA formation by ATL cells, suggesting the involvement of vimentin in anchoring ATL cells to the feeder layer. Ad-MCA formation by ATL cells on a layer of epithelial-like feeder cells may mimic critical events that occur in metastatic colonization.
|
巻・号 |
357(1)
|
ページ |
355-363
|
公開日 |
2015-2-1
|
DOI |
10.1016/j.canlet.2014.11.055
|
PII |
S0304-3835(14)00740-X
|
PMID |
25448402
|
MeSH |
Apoptosis / physiology
HEK293 Cells
Humans
Hyaluronan Receptors / metabolism*
Jurkat Cells
Leukemia-Lymphoma, Adult T-Cell / metabolism*
Leukemia-Lymphoma, Adult T-Cell / pathology*
NF-kappa B / metabolism*
Neoplastic Stem Cells / metabolism*
Neoplastic Stem Cells / pathology
Tumor Cells, Cultured
Vimentin / metabolism*
|
IF |
7.36
|
引用数 |
10
|
WOS 分野
|
ONCOLOGY
|
リソース情報 |
ヒト・動物細胞 |
1C3IKEI(RCB0797) |