Cancer Stem Cell-Like Cells Derived from Malignant Peripheral Nerve Sheath Tumors

Spyra, Melanie; Kluwe, Lan; Hagel, Christian; Nguyen, Rosalyn; Panse, Jens; Kurtz, Armin; Mautner, Victor; Rabkin, Samuel D.; Demestre, Maria

doi:10.1371/journal.pone.0021099

Cited by 43 publications

(47 citation statements)

References 17 publications

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“…With regards to CSCs conflicting reports abound. Downregulation of NCAM in CSC populations is observed in peripheral neural sheath tumors 114 in contrast to reports in GBM where NCAM expression correlates with Olig 2 expression, a well-known GBM stem cell marker. 113 Additional studies are required to further address these issues, better define the role of NCAM in microenvironmental regulation and clarify the expression of NCAM in CSCs and other tumor microenvironment cells.…”

Section: Ncamcontrasting

confidence: 68%

The malignant social network

Hale

Lathia

2012

Cell Adhesion & Migration

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Tumors contain a vastly complicated cellular network that relies on local communication to execute malignant programs. The molecular cues that are involved in cell-cell adhesion orchestrate large-scale tumor behaviors such as proliferation and invasion. We have recently begun to appreciate that many tumors contain a high degree of cellular heterogeneity and are organized in a cellular hierarchy, with a cancer stem cell (CSC) population identified at the apex in multiple cancer types. CSCs reside in unique microenvironments or niches that are responsible for directing their behavior through cellular interactions between CSCs and stromal cells, generating a malignant social network. Identifying cell-cell adhesion mechanisms in this network has implications for the basic understanding of tumorigenesis and the development of more effective therapies. In this review, we will discuss our current understanding of cell-cell adhesion mechanisms used by CSCs and how these local interactions have global consequences for tumor biology.

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Section: Ncamcontrasting

confidence: 68%

The malignant social network

Hale

Lathia

2012

Cell Adhesion & Migration

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“…These results suggest that the tumors originated from neural crest cells, such as Schwann cells or striated muscle cells, and some contained possible cancer stem cells because nestin, NGFR, and CD133 are stem cell markers. 2,3,14,17 The ability of neural crest cells to differentiate into a diverse range of cell types explains the expression of Schwannian and striated muscle markers in the neoplastic cells. The cytoplasmic granules in the neoplastic cells were positive for LC3, p62, NBR1, and ubiquitin.…”

Section: Discussionmentioning

confidence: 99%

The Origin and Role of Autophagy in the Formation of Cytoplasmic Granules in Canine Lingual Granular Cell Tumors

et al. 2014

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Granular cell tumors (GCTs) are histologically characterized by polygonal neoplastic cells with abundant eosinophilic cytoplasmic granules. In humans, these cells are considered to be derived from Schwann cells, and the cytoplasmic granules are assumed to be autophagosomes or autophagolysosomes. However, the origin and nature of the cytoplasmic granules in canine GCTs have not been well characterized. The present study examined 9 canine lingual GCTs using immunohistochemistry, transmission electron microscopy (TEM), and cell culture and xenotransplantation experiments. In some cases, the tumor cells expressed S100, CD133, and desmin. The cytoplasmic granules were positive for LC3, p62, NBR1, and ubiquitin. TEM revealed autophagosome-like structures in the cytoplasm of the granule-containing cells. The cultured GCT cells were round to spindle shaped and expressed S100, nestin, Melan-A, CD133, LC3, p62, NBR1, and ubiquitin, suggesting that they were of neural crest origin, redifferentiated into melanocytes, and exhibited upregulated autophagy. The xenotransplanted tumors consisted of spindle to polygonal cells. Only a few cells contained cytoplasmic granules, and some had melanin pigments in their cytoplasm. The xenotransplanted cells expressed S100, nestin, Melan-A, and CD133. P62 and ubiquitin were detected, regardless of the presence or absence of cytoplasmic granules, while LC3 and NBR1 were detected only in the neoplastic cells containing cytoplasmic granules. These findings suggest that some xenotransplanted cells redifferentiated into melanocytes and that autophagy was upregulated in the cytoplasmic granule-containing cells. In conclusion, canine lingual GCTs originate from the neural crest and develop cytoplasmic granules via autophagy. In addition, the microenvironment of GCT cells affects their morphology.

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“…Further studies of both CTVT and DFTD from a CSC perspective may also provide insight to their respective analogous human cancers (as currently understood), where the CSC model has been investigated. Some data, while equivocal and subject of some discussion, suggest that certain neural crest cancers (e.g., melanoma, neuroblastoma) may have a CSC component [33,[52][53][54], and recent data indicates that putative CSCs may exist in certain MPNST cell lines [55]. The neural crest origin for DFTD implies that a similar evaluation for CSCs may be of interest to biologists investigating such cancers.…”

Section: Discussion and Possible Utility Of A Csc Approachmentioning

confidence: 99%

Concise Review: Transmissible Animal Tumors as Models of the Cancer Stem-Cell Process

O’Neill¹

2011

Stem Cells

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Tasmanian devil facial tumor disease (DFTD) and canine transmissible venereal tumor (CTVT) are highly unusual cancers capable of being transmitted between animals as an allograft. The concept that these tumors represent a cancer stem-cell process has never been formally evaluated. For each, evidence of self-renewal is found in the natural history of these tumors in the wild, tumor initiation in recipient animals, and serial transplantation studies. Additional data for stem-cell-specific genes and markers in DFTD also exist. Although both tumor types manifest as undifferentiated cancers, immunocytohistochemistry supports a histiocytic phenotype for CTVT and a neural crest origin, possibly a Schwann-cell phenotype, for DFTD. In these data, differential expression of lineage markers is seen which may suggest some capacity for differentiation toward a heterogeneous variety of cell types. It is proposed that DFTD and CTVT may represent and may serve as models of the cancer stem-cell process, but formal investigation is required to clarify this. Appreciation of any such role may act as a stimulus to ongoing research in the pathology of DFTD and CTVT, including further characterization of their origin and phenotype and possible therapeutic approaches. Additionally, they may provide valuable models for future studies of their analogous human cancers, including any putative CSC component.

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Cancer Stem Cell-Like Cells Derived from Malignant Peripheral Nerve Sheath Tumors

Cited by 43 publications

References 17 publications

The malignant social network

The malignant social network

The Origin and Role of Autophagy in the Formation of Cytoplasmic Granules in Canine Lingual Granular Cell Tumors

Concise Review: Transmissible Animal Tumors as Models of the Cancer Stem-Cell Process

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