A comparative review of the immunobiology of murine neuroblastoma and human neuroblastoma

Ziegler, Moritz M.; Ishizu, Hideki; Nagabuchi, E; Takada, Naoyuki; Arya, Gajra

doi:10.1002/(sici)1097-0142(19970501)79:9<1757::aid-cncr18>3.0.co;2-x

Cited by 17 publications

(1 citation statement)

References 53 publications

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“…Despite many previous studies which have focused on morphological and biochemical differences within NB cells, the cellular heterogeneity of NB has not been resolved in detail 13 , 14 . While transgenic, syngeneic or xenograft mouse models represent clinically relevant tools for studying NB growth and metastasis 15 – 18 , cell-based models are the system of choice to determine tumor cell characteristics and to identify pharmacological candidates and assess their efficacy 19 , 20 . In NB in vitro models, commonly three different cell types have been distinguished on a morphological basis: “N-type” showing properties of noradrenergic neurons, “S-type” (substrate-adherent) as a mesenchymal subset showing fibronectin and vimentin expression and the intermediate “I-type” with a mixed expression pattern 21 .…”

Section: Introductionmentioning

confidence: 99%

Surface marker profiling of SH-SY5Y cells enables small molecule screens identifying BMP4 as a modulator of neuroblastoma differentiation

Ferlemann

Menon

Condurat

et al. 2017

Sci Rep

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Neuroblastoma is the most common extra-cranial solid tumor in children. Its broad spectrum of clinical outcomes reflects the underlying inherent cellular heterogeneity. As current treatments often do not lead to tumor eradication, there is a need to better define therapy-resistant neuroblastoma and to identify new modulatory molecules. To this end, we performed the first comprehensive flow cytometric characterization of surface molecule expression in neuroblastoma cell lines. Exploiting an established clustering algorithm (SPADE) for unbiased visualization of cellular subsets, we conducted a multiwell screen for small molecule modulators of neuroblastoma phenotype. In addition to SH-SY5Y cells, the SH-EP, BE(2)-M17 and Kelly lines were included in follow-up analysis as in vitro models of neuroblastoma. A combinatorial detection of glycoprotein epitopes (CD15, CD24, CD44, CD57, TrkA) and the chemokine receptor CXCR4 (CD184) enabled the quantitative identification of SPADE-defined clusters differentially responding to small molecules. Exposure to bone morphogenetic protein (BMP)-4 was found to enhance a TrkAhigh/CD15−/CD184− neuroblastoma cellular subset, accompanied by a reduction in doublecortin-positive neuroblasts and of NMYC protein expression in SH-SY5Y cells. Beyond yielding novel marker candidates for studying neuroblastoma pathology, our approach may provide tools for improved pharmacological screens towards developing novel avenues of neuroblastoma diagnosis and treatment.

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Section: Introductionmentioning

confidence: 99%

Surface marker profiling of SH-SY5Y cells enables small molecule screens identifying BMP4 as a modulator of neuroblastoma differentiation

Ferlemann

Menon

Condurat

et al. 2017

Sci Rep

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Murine models for experimental therapy of pediatric solid tumors with poor prognosis

Beltinger

Debatin

2001

Int. J. Cancer

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Novel therapeutic strategies are required for pediatric solid tumors with poor prognosis such as metastasizing neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma. A prerequisite for the development of such new therapies is the availability of murine models. To be useful for therapeutic studies, these models should not only recapitulate the genetic alterations characteristic of the human disease but should also mimic the metastatic process and the response to current therapy, both of which ultimately determine the fate of children with these tumors. This review scrutinizes the utility of existing murine models of neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma for investigating novel therapies. Much experience has been gained with both syngeneic and xenogeneic transplantable models of these tumors, while transgenic and knockout mice are just beginning to be available for therapeutic investigations. Modeling the genetic aberrations characterizing these tumors may provide faithful models for therapeutic studies in the future.Key words: mouse model; neuroblastoma; rhabdomyosarcoma; Ewing's sarcoma; therapy In contrast to adults, most children with localized solid tumors can be cured today. However, subsets of pediatric solid tumors still carry a poor prognosis. Besides brain tumors, which will not be considered in this review because of their unique features, these tumors include metastatic neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma. As a paradigm, the dismal prognosis for advanced-stage neuroblastoma has not changed much for decades. While current therapy is largely based on clinical studies of combined chemo-and radiotherapy, the development of new therapies has to rely on clinically relevant murine models of these tumors. This is especially important in pediatric oncology, given the low number of children eligible for phase I trials. 1 The purpose of this review is to discuss the utility of existing murine models of poor-prognosis extracranial pediatric solid tumors for investigating novel therapies. Available mouse models for neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma are reviewed. These tumors have been selected because of their wellcharacterized genetic alterations amenable to mouse modeling and molecular therapeutic strategies. THE "IDEAL" MURINE MODEL OF A SOLID TUMOR FOR THERAPEUTIC RESEARCHThe general limitations of therapeutic research with both transplantable tumor models (syngeneic and xenogeneic) and "spontanously" arising tumors in transgenic or knockout mice have recently been reviewed. 2,3 The characteristics of an "ideal" murine model of a solid tumor have been well defined, as follows:1. Some tumors, especially tumors of childhood, are well described on the genetic level and show characteristic genetic alterations. These changes should obviously be present in the tumor model if the experimental approach targets these changes. However, if the therapy to be tested does not specifically target the etiologic mutation but the ensuing molecular pathology, mouse models that show...

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Experimental Therapeutics and Preclinical Models

Peterson¹,

Houghton²

Pediatric Oncology

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A comparative review of the immunobiology of murine neuroblastoma and human neuroblastoma

Cited by 17 publications

References 53 publications

Surface marker profiling of SH-SY5Y cells enables small molecule screens identifying BMP4 as a modulator of neuroblastoma differentiation

Surface marker profiling of SH-SY5Y cells enables small molecule screens identifying BMP4 as a modulator of neuroblastoma differentiation

Murine models for experimental therapy of pediatric solid tumors with poor prognosis

Experimental Therapeutics and Preclinical Models

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