Human neuroblastoma stem cells

Ross, Robert A.; Spengler, Barbara A.

doi:10.1016/j.semcancer.2006.04.006

Cited by 109 publications

(120 citation statements)

References 36 publications

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“…Although the distinct cell morphology of DisNB variants (I-like-type phenotype) and the relatively high expression of CD133 and CD24 by these cells support the possibility that they are NB stem cells, 46 -48 the relatively low expression of c-Kit 46 and the absence of CD34 23 and CD44 49 expression by these cells cast a shadow of doubt on this possibility. Previous studies from our laboratory and those of others have demonstrated that the chemokine receptors CXCR4, CXCR5, CXCR6, and CX3CR1 function as promalignancy factors in NB.…”

Section: Discussionmentioning

confidence: 99%

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Lung-Residing Metastatic and Dormant Neuroblastoma Cells

Botzer

Maman

Sagi‐Assif

et al. 2011

The American Journal of Pathology

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The mechanism by which dormant tumor cells can begin growing after long periods of inactivity and accelerate disease recurrence is poorly understood. The present study characterizes dormant neuroblastoma (NB) cells, as well as metastatic cells, which reside in the same organ microenvironment. A xenograft model of human NB consisting of variants that generate nonmetastatic local tumors in the orthotopic inoculation site and variants that generate lung metastatic NB (MetNB) cells was developed in our laboratory. The present study shows that lungs of mice inoculated with nonmetastatic NB variants contain disseminated neuroblastoma (DisNB) human cells. Both DisNB and MetNB variants expressed a similar tumorigenicty phenotype in vivo, whereas the MetNB variants produced a heavy metastatic load and the DisNB variants produced no or little metastasis. A comparative in vitro characterization of MetNB and DisNB cells revealed similarities and differences. DisNB, but not MetNB cells, expressed the minimal residual disease markers PHOX2B and TH. MetNB cells demonstrated higher migratory capacity, an elevated matrix metalloproteinase (MMP) secretion, and a higher constitutive phosphorylation of extracellular signalregulated kinase (ERK) than DisNB cells. We suggest that characteristics common to both MetNB and DisNB cells were acquired relatively early in the metastatic process and the characteristics that differ between these variants were acquired later. We hypothesize that the DisNB cells are metastasis precursors, which may progress toward metastasis under certain microenvironmental conditions. Neuroblastoma (NB) is the most common extracranial solid tumor in children comprising 8% to 10% of all childhood cancers. More than half of these patients have a metastatic disease at diagnosis. 1-3 NB cells disseminate either by hematogenous spread, producing metastasis most frequently in bone marrow, bone, liver, and skin, or by lymphatic spread to regional and distant lymph nodes. 4 Lung metastases are considered a terminal event representing a widely disseminated metastatic disease. [5][6] Approximately 50% of children with high-risk NB that complete consolidation therapy develop early or late relapse, often from minimal residual disease in the form of circulating NB cells or micrometastases. 7 Most of the children with NB present metastatic disease at diagnosis with poor outcome, despite intensive treatment protocols. 8 The presence of circulating NB cells and/or NB micrometastasis may indicate a significant high-risk disease. 9 However, the question whether NB micrometastases develop into metastatic disease is yet to be answered.Previous studies from our laboratory were aimed to identify molecular pathways that are involved in NB metastasis. We focus on the cross talk between metastatic NB cells and components of their microenvironment, and on the downstream effects of such interactions.We suggested that NB cells might use chemokinechemokine receptor axes in their progression to metastasis. For example the CXCR4 -CXCL12 10 ...

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Section: Discussionmentioning

confidence: 99%

“…*Human neuroblastoma (NB) cell lines present three cell phenotypic subtypes, the neuroblastic (N), the substrate adherent (S), and the intermediate (I) subtypes (have recently been proposed as NB stem cells) 46 .…”

Section: Discussionmentioning

confidence: 99%

Lung-Residing Metastatic and Dormant Neuroblastoma Cells

Botzer

Maman

Sagi‐Assif

et al. 2011

The American Journal of Pathology

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“…Neuroblastoma arises from the cells that normally make up an embryonic structure called the neural crest (5). The neural crest cells consist of multipotent and migratory cell populations that give rise to diverse cell lineages including Schwann cells, melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons, and glia (5).…”

Section: Mitosis | Cd133mentioning

confidence: 99%

“…Thus, neural crest cells serve as multipotent stem cells that differentiate into mature neural tissues. It is now suspected that the multipotent neural crest cells might contribute to neuroblastoma tumorigenesis due to aberrant MYCN expression (5).…”

Section: Mitosis | Cd133mentioning

confidence: 99%

Evidence of asymmetric cell division and centrosome inheritance in human neuroblastoma cells

Izumi

Kaneko

2012

Proc. Natl. Acad. Sci. U.S.A.

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Asymmetric cell division (ACD) is believed to be a physiological event that occurs during development and tissue homeostasis in a large variety of organisms. ACD produces two unequal daughter cells, one of which resembles a multipotent stem and/or progenitor cell, whereas the other has potential for differentiation. Although recent studies have shown that the balance between self-renewal and differentiation potentials is precisely controlled and that alterations in the balance may lead to tumorigenesis in Drosophila neuroblasts, it is largely unknown whether human cancer cells directly show ACD in an evolutionarily conserved manner. Here, we show that the conserved polarity/spindle protein NuMA is preferentially localized to one side of the cell cortex during cell division, generating unequal inheritance of fate-altering molecules in human neuroblastoma cell lines. We also show that the cells with a single copy of MYCN showed significantly higher percentages of ACD than those with MYCN amplification. Moreover, suppression of MYCN in MYCN-amplified cells caused ACD, whereas expression of MYCN in MYCN-nonamplified cells enhanced symmetric cell division. Furthermore, we demonstrate that centrosome inheritance follows a definite rule in ACD: The daughter centrosome with younger mother centriole is inherited to the daughter cell with NuMA preferentially localized to the cell cortex, whereas the mother centrosome with the older mother centriole migrates to the other daughter cell. Thus, the mechanisms of cell division of ACD or symmetric cell division and centrosome inheritance are recapitulated in human cancer cells, and these findings may facilitate studies on cancer stem cells.

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“…For example, in one study <100 cells of the identified tumorigenic subpopulation in a breast cancer model were required to form tumors [9]. Highly tumorigenic cells have also been described in other cancers such as brain tumors [10], melanoma [11], hepatocellular carcinoma [12] and neuroblastoma [13]. Although a recent study questioned the use of xenograft models for these tumorigenicity studies [14], the fact that only a subset of tumor cells are efficient at establishing a tumor is undeniable.…”

mentioning

confidence: 99%

Can less really be more? Using lessons from leukemia and cancer stem cells to make sense of oral maintenance for metastatic sarcoma

Cripe

2007

Pediatric Blood & Cancer

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Human neuroblastoma stem cells

Cited by 109 publications

References 36 publications

Lung-Residing Metastatic and Dormant Neuroblastoma Cells

Lung-Residing Metastatic and Dormant Neuroblastoma Cells

Evidence of asymmetric cell division and centrosome inheritance in human neuroblastoma cells

Can less really be more? Using lessons from leukemia and cancer stem cells to make sense of oral maintenance for metastatic sarcoma

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