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Anchorage-dependent multicellular aggregate formation induces CD44 high cancer stem cell-like ATL cells in an NF-kappa B- and vimentin-dependent manner

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Title: Anchorage-dependent multicellular aggregate formation induces CD44 high cancer stem cell-like ATL cells in an NF-kappa B- and vimentin-dependent manner
Authors: Miyatake, Yukiko Browse this author →KAKEN DB
Sheehy, Noreen Browse this author
Ikeshita, Shunji Browse this author
Hall, William W. Browse this author
Kasahara, Masanori Browse this author →KAKEN DB
Keywords: Cancer stem cells
Coculture
CD44
Vimentin, ATL
Issue Date: 1-Feb-2015
Publisher: Elsevier Ireland
Journal Title: Cancer letters
Volume: 357
Issue: 1
Start Page: 355
End Page: 363
Publisher DOI: 10.1016/j.canlet.2014.11.055
PMID: 25448402
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-kappa B activity. Blockade of the NF kappa B 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. (c) 2014 Elsevier Ireland Ltd. All rights reserved.
Type: article (author version)
URI: http://hdl.handle.net/2115/58276
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 宮武 由甲子

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