| RRC ID |
44333
|
| Author |
Miyatake Y, Oliveira AL, Jarboui MA, Ota S, Tomaru U, Teshima T, Hall WW, Kasahara M.
|
| Title |
Protective roles of epithelial cells in the survival of adult T-cell leukemia/lymphoma cells.
|
| Journal |
Am J Pathol
|
| Abstract |
Adult T-cell leukemia/lymphoma (ATL) is a highly invasive and intractable T-cell malignancy caused by human T-cell leukemia virus-1 infection. We demonstrate herein that normal tissue-derived epithelial cells (NECs) exert protective effects on the survival of leukemic cells, which may partially account for high resistance to antileukemic therapies in patients with ATL. Viral gene-silenced, ATL-derived cell lines (ATL cells) dramatically escaped from histone deacetylase inhibitor-induced apoptosis by direct co-culture with NECs. Adhesions to NECs suppressed p21(Cip1) expression and increased a proportion of resting G0/G1 phase cells in trichostatin A (TSA)-treated ATL cells. ATL cells adhering to NECs down-regulated CD25 expression and enhanced vimentin expression, suggesting that most ATL cells acquired a quiescent state by cell-cell interactions with NECs. ATL cells adhering to NECs displayed highly elevated expression of the cancer stem cell marker CD44. Blockade of CD44 signaling diminished the NEC-conferred resistance of ATL cells to TSA-induced apoptosis. Co-culture with NECs also suppressed the expression of NKG2D ligands on TSA-treated ATL cells, resulting in decreased natural killer cell-mediated cytotoxicity. Combined evidence suggests that interactions with normal epithelial cells augment the resistance of ATL cells to TSA-induced apoptosis and facilitate immune evasion by ATL cells.
|
| Volume |
182(5)
|
| Pages |
1832-42
|
| Published |
2013-5-1
|
| DOI |
10.1016/j.ajpath.2013.01.015
|
| PII |
S0002-9440(13)00099-0
|
| PMID |
23474084
|
| MeSH |
Adult
Apoptosis / drug effects
Cell Adhesion / drug effects
Cell Communication / drug effects
Cell Cycle / drug effects
Cell Line, Tumor
Cell Separation
Cell Survival / drug effects
Coculture Techniques
Cytoprotection* / drug effects
Epithelial Cells / drug effects
Epithelial Cells / metabolism
Epithelial Cells / pathology*
Histone Deacetylase Inhibitors / pharmacology
Humans
Hyaluronan Receptors / metabolism
Hydroxamic Acids / pharmacology
Intracellular Space / drug effects
Intracellular Space / metabolism
Leukemia-Lymphoma, Adult T-Cell / pathology*
Ligands
NK Cell Lectin-Like Receptor Subfamily K / metabolism
Tumor Stem Cell Assay
|
| IF |
3.491
|
| Times Cited |
14
|
|
WOS Category
|
PATHOLOGY
|
| Resource |
| Human and Animal Cells |
1C3IKEI(RCB0797) |
