Cancer stem cells in leukemia, recent advances

Zou, Gang

doi:10.1002/jcp.21140

Cited by 35 publications

(27 citation statements)

References 49 publications

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“…Such associations have repeatedly been shown for CD44/CD44v (39,40,43,44) and could be shown for ASML wt but not ASML-CD44v rsc cells. We noted an increased association between CD44v6 and c-Src in ASML cells, which was accompanied by increased activation of the focal adhesion kinase, 5 which can trigger PI3K activation. It also has been described that c-met supports tumor cell survival via PI3K/Akt activation (45,46) and that c-met interacts with CD44v6 via hepatocyte growth factor/scatter factor binding (23).…”

Section: Cd44v and Apoptosis Protectionmentioning

confidence: 72%

“…Restoring CD44v expression in ASML-CD44v kd clones suffices to rescue the metastatic potential but not apoptosis 5 T. Jung, unpublished finding. resistance.…”

Section: Cd44v and Apoptosis Protectionmentioning

confidence: 89%

“…Notably, c-met activity is significantly reduced in ASML-CD44v kd cells. 5 Taken together, the ASML matrix (see below) might act as a reservoir for growth factors such as hepatocyte growth factor/scatter factor (47). Concomitantly, appropriately assembled hyaluronan could act as the initial trigger leading to CD44 clustering.…”

Section: Cd44v and Apoptosis Protectionmentioning

confidence: 99%

“…Meanwhile, there is ample evidence for the importance of CD44v in tumor progression (2,3). In addition, CD44 has been recognized as a cancer-initiating cell (CIC) marker in several types of cancer (4,5). Notably, CIC are supposed to act as initiators of metastatic spread (4,6).…”

Section: Introductionmentioning

confidence: 99%

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CD44 Variant Isoforms Promote Metastasis Formation by a Tumor Cell-Matrix Cross-talk That Supports Adhesion and Apoptosis Resistance

Klingbeil

Marhaba

Jung

et al. 2009

Molecular Cancer Research

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CD44 designates a large family of proteins with a considerable structural and functional diversity, which are generated from one gene by alternative splicing. As such, the overexpression of CD44 variant isoform (CD44v) has been causally related to the metastatic spread of cancer cells. To study the underlying mechanism, stable knockdown clones with deletion of exon v7 containing CD44 isoforms (CD44v kd ) of the highly metastatic rat adenocarcinoma line BSp73ASML (ASML wt ) were established. ASML-CD44v kd clones hardly form lung metastases after intrafootpad application and the metastatic load in lymph nodes is significantly reduced. Rescuing, albeit at a reduced level, CD44v expression in ASML-CD44v kd cells (ASML-CD44v rsc ) restores the metastatic potential. The following major differences in ASML wt , ASML-CD44v kd , and ASML-CD44v rsc clones were observed: (a) ASML wt cells produce and assemble a matrix in a CD44v-dependent manner, which supports integrin-mediated adhesion and favors survival. This feature is lost in the ASML-CD44v kd cells. (b) CD44v cross-linking initiates phosphatidylinositol 3-kinase/Akt activation in ASML wt cells. Accordingly, apoptosis resistance is strikingly reduced in ASML-CD44v kd cells. The capacity to generate an adhesive matrix but not apoptosis resistance is restored in ASML-CD44v rsc cells. These data argue for a 2-fold effect of CD44v on metastasis formation: CD44v-mediated matrix formation is crucial for the settlement and growth at a secondary site, whereas apoptosis resistance supports the efficacy of metastasis formation.

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Section: Cd44v and Apoptosis Protectionmentioning

confidence: 72%

“…Restoring CD44v expression in ASML-CD44v kd clones suffices to rescue the metastatic potential but not apoptosis 5 T. Jung, unpublished finding. resistance.…”

Section: Cd44v and Apoptosis Protectionmentioning

confidence: 89%

Section: Cd44v and Apoptosis Protectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

CD44 Variant Isoforms Promote Metastasis Formation by a Tumor Cell-Matrix Cross-talk That Supports Adhesion and Apoptosis Resistance

Klingbeil

Marhaba

Jung

et al. 2009

Molecular Cancer Research

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“…CD44 contributes to HSC-and leukemia-initiating cell homing (4,50), the feature of which is used for HSC mobilization (17,51) and leukemia-initiating cell dislodgment by anti-CD44, driving the latter into differentiation and apoptosis (5,6). Because antiCD49d also promotes HSC and leukemia cell mobilization (16,52), and a CD44-CD49d cooperation additionally supports proliferation and apoptosis resistance (23,53), we assumed that a blockade of both CD44 and CD49d may be a more efficient therapeutic.…”

Section: Discussionmentioning

confidence: 99%

Cooperativity of CD44 and CD49d in Leukemia Cell Homing, Migration, and Survival Offers a Means for Therapeutic Attack

Singh

Erb

Zöller

2013

The Journal of Immunology

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A CD44 blockade drives leukemic cells into differentiation and apoptosis by dislodging from the osteogenic niche. Because anti-CD49d also supports hematopoietic stem cell mobilization, we sought to determine the therapeutic efficacy of a joint CD49d/CD44 blockade. To unravel the underlying mechanism, the CD49d− EL4 lymphoma was transfected with CD49d or point-mutated CD49d, prohibiting phosphorylation and FAK binding; additionally, a CD44− Jurkat subline was transfected with murine CD44, CD44 with a point mutation in the ezrin binding site, or with cytoplasmic tail–truncated CD44. Parental and transfected EL4 and Jurkat cells were evaluated for adhesion, migration, and apoptosis susceptibility in vitro and in vivo. Ligand-binding and Ab-blocking studies revealed CD44–CD49d cooperation in vitro and in vivo in adhesion, migration, and apoptosis resistance. The cooperation depends on ligand-induced proximity such that both CD44 and CD49d get access to src, FAK, and paxillin and via lck to the MAPK pathway, with the latter also supporting antiapoptotic molecule liberation. Accordingly, synergisms were only seen in leukemia cells expressing wild-type CD44 and CD49d. Anti-CD44 together with anti-CD49d efficiently dislodged EL4-CD49d/Jurkat-CD44 in bone marrow and spleen. Dislodging was accompanied by increased apoptosis susceptibility that strengthened low-dose chemotherapy, the combined treatment most strongly interfering with metastatic settlement and being partly curative. Ab treatment also promoted NK and Ab-dependent cellular cytotoxicity activation, which affected leukemia cells independent of CD44/CD49d tail mutations. Thus, mostly owing to a blockade of joint signaling, anti-CD44 and anti-CD49d hamper leukemic cell settlement and break apoptosis resistance, which strongly supports low-dose chemotherapy.

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A flow‐through microfluidic chip for continuous dielectrophoretic separation of viable and non‐viable human T‐cells

et al. 2021

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Effective methods for rapid sorting of cells according to their viability are critical in T cells based therapies to prevent any risk to patients. In this context, we present a novel microfluidic device that continuously separates viable and non-viable T-cells according to their dielectric properties. A dielectrophoresis (DEP) force is generated by an array of castellated microelectrodes embedded into a microfluidic channel with a single inlet and two outlets; cells subjected to positive DEP forces are drawn toward the electrodes array and leave from the top outlet, those subjected to negative DEP forces are repelled away from the electrodes and leave from the bottom outlet. Computational fluid dynamics is used to predict the device separation efficacy, according to the applied alternative current (AC) frequency, at which the cells move from/to a negative/positive DEP region and the ionic strength of the suspension medium. The model is used to support the design of the operational conditions, confirming a separation efficiency, in terms of purity, of 96% under an applied AC frequency of 1.5 × 10 6 Hz and a flow rate of 20 μl/h. This work represents the first example of effective continuous sorting of viable and non-viable human T-cells in a single-inlet microfluidic chip, paving the way for lab-on-a-chip applications at the point of need.

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Cancer stem cells in leukemia, recent advances

Cited by 35 publications

References 49 publications

CD44 Variant Isoforms Promote Metastasis Formation by a Tumor Cell-Matrix Cross-talk That Supports Adhesion and Apoptosis Resistance

CD44 Variant Isoforms Promote Metastasis Formation by a Tumor Cell-Matrix Cross-talk That Supports Adhesion and Apoptosis Resistance

Cooperativity of CD44 and CD49d in Leukemia Cell Homing, Migration, and Survival Offers a Means for Therapeutic Attack

A flow‐through microfluidic chip for continuous dielectrophoretic separation of viable and non‐viable human T‐cells

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