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
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 4.069
Times Cited 9
Human and Animal Cells