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

Miyatake, Yukiko; Sheehy, Noreen; Ikeshita, Shunji; Hall, William W.; Kasahara, Masanori

doi:10.1016/j.canlet.2014.11.055

Cited by 16 publications

(10 citation statements)

References 46 publications

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“…A recent study of adult T-cell leukemia (ATL) demonstrated that ATL cells grown on epithelial cells form anchorage-dependent multicellular aggregate with a subpopulation of cancer stem cells with high CD44 expression [38]. The results of this study have two interesting implications; first, it demonstrated that cancer stem cells in ATL can be induced by microenvironmental interactions; and second, it validated the significance of CD44 in the aggressive, highly invasive and metastatic phenotype characteristic of ATL cancer stem cells.…”

Section: Expression Profile Of Cd44 In Different Cellsmentioning

confidence: 99%

Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine

Mattheolabakis

Milane

Singh

et al. 2015

Journal of Drug Targeting

472

310

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Cluster of differentiation-44 (CD44) is a ubiquitously present glycoprotein on the surface of mammalian cells that plays a significant role in a number of biological functions. Since the discovery that the receptor is over-expressed in a variety of solid tumors, such as pancreatic, breast and lung cancer, many studies have focused on methods for targeting CD44 in an attempt to improve drug delivery and discrimination between healthy and malignant tissue, while reducing residual toxicity and off-target accumulation. In this review, we describe CD44 receptor biology and its involvement in the different stages of tumor growth and metastasis, as well as methods currently used for targeting the receptor. Hyaluronic acid, the primary CD44 binding molecule, has proved a significant ally in developing nanocarriers that demonstrate preferential tumor accumulation and increased cell uptake. We outline a number of research approaches from the current literature that take advantage of hyaluronic acid's targeting ability and describe the possible advantages for each approach. The value of CD44 targeting can be easily appreciated from the number of different approaches that have reached clinical trials.

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Section: Expression Profile Of Cd44 In Different Cellsmentioning

confidence: 99%

Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine

Mattheolabakis

Milane

Singh

et al. 2015

Journal of Drug Targeting

472

310

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“…Several reports suggested importance of interaction with normal epithelial cells and mesenchymal stem cells. [121][122][123] Furthermore, involvement of angiogenesis and fibroblast-derived osteopontin has been suggested in proliferation and survival, as well as possible roles of exosomes produced by ATL cells. [124][125][126] In this regard, a possible role of mutations of Notch1 signaling 70,87 appears to deserve further examination.…”

Section: Summary and Perspectivesmentioning

confidence: 99%

Adult T-cell leukemia: molecular basis for clonal expansion and transformation of HTLV-1–infected T cells

Watanabe

2017

Blood

144

117

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Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) that develops through a multistep carcinogenesis process involving 5 or more genetic events. We provide a comprehensive overview of recently uncovered information on the molecular basis of leukemogenesis in ATL. Broadly, the landscape of genetic abnormalities in ATL that include alterations highly enriched in genes for T-cell receptor–NF-κB signaling such as PLCG1, PRKCB, and CARD11 and gain-of function mutations in CCR4 and CCR7. Conversely, the epigenetic landscape of ATL can be summarized as polycomb repressive complex 2 hyperactivation with genome-wide H3K27 me3 accumulation as the basis of the unique transcriptome of ATL cells. Expression of H3K27 methyltransferase enhancer of zeste 2 was shown to be induced by HTLV-1 Tax and NF-κB. Furthermore, provirus integration site analysis with high-throughput sequencing enabled the analysis of clonal composition and cell number of each clone in vivo, whereas multicolor flow cytometric analysis with CD7 and cell adhesion molecule 1 enabled the identification of HTLV-1–infected CD4+ T cells in vivo. Sorted immortalized but untransformed cells displayed epigenetic changes closely overlapping those observed in terminally transformed ATL cells, suggesting that epigenetic abnormalities are likely earlier events in leukemogenesis. These new findings broaden the scope of conceptualization of the molecular mechanisms of leukemogenesis, dissecting them into immortalization and clonal progression. These recent findings also open a new direction of drug development for ATL prevention and treatment because epigenetic marks can be reprogrammed. Mechanisms underlying initial immortalization and progressive accumulation of these abnormalities remain to be elucidated.

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“…1B). The ATL-CR and ATL-TH cell lines were established from patients with ATL and viral gene expression is silenced in these cells (Miyatake et al, 2013, 2015). The status of HBZ expression in the ATL-CR and ATL-TH cell lines was not investigated.…”

Section: Resultsmentioning

confidence: 99%

Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles

et al. 2016

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The human T-cell leukaemia virus type 1 and type 2 (HTLV-1/HTLV-2) antisense proteins HBZ and APH-2 play key roles in the HTLV lifecycles and persistence in the host. Nuclear Factors Associated with double-stranded RNA (NFAR) proteins NF90/110 function in the lifecycles of several viruses and participate in host innate immunity against infection and oncogenesis. Using GST pulldown and co-immunoprecipitation assays we demonstrate specific novel interactions between HBZ/APH-2 and NF90/110 and characterised the protein domains involved. Moreover we show that NF90/110 significantly enhance Tax mediated LTR activation, an effect that was abolished by HBZ but enhanced by APH-2. Additionally we found that HBZ and APH-2 modulate the promoter activity of survivin and are capable of antagonising NF110-mediated survivin activation. Thus interactions between HTLV antisense proteins and the NFAR protein family have an overall positive impact on HTLV infection. Hence NFARs may represent potential therapeutic targets in HTLV infected cells.

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

Cited by 16 publications

References 46 publications

Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine

Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine

Adult T-cell leukemia: molecular basis for clonal expansion and transformation of HTLV-1–infected T cells

Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles

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