Overactivation of Ras signaling pathway in CD133+ MPNST cells

Borrego-Diaz, Emma; Terai, Kaoru; Lialyte, Kristina; Wise, Amanda L.; Esfandyari, Tuba; Behbod, Fariba; Mautner, Victor; Spyra, Melanie; Taylor, Sarah; Parada, Luis F.; Upadhyaya, Meena; Farassati, Faris

doi:10.1007/s11060-012-0852-1

Cited by 19 publications

(14 citation statements)

References 67 publications

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“…5,35 The expression levels of the neural crest stem cell markers nestin and NGFR observed in the present study suggest that canine MPNSTs contain neural crest stem cells or cancer stem-like cells, which might be useful treatment targets. Classifying MPNSTs and PWTs as ''soft tissue sarcomas'' together with other spindle cell tumors that arise in soft tissue will prevent treatments for MPNSTs and PWTs from being developed and, hence, their prognosis will never improve.…”

Section: Cluster Analysesmentioning

confidence: 60%

The Effects of Tumor Location on Diagnostic Criteria for Canine Malignant Peripheral Nerve Sheath Tumors (MPNSTs) and the Markers for Distinction Between Canine MPNSTs and Canine Perivascular Wall Tumors

2013

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Canine malignant peripheral nerve sheath tumors (MPNSTs) occur not only in the peripheral nervous system (PNS) but also in soft tissue and various organs (non-PNS). The most important diagnostic criterion is proof of peripheral nerve sheath origin. This is difficult in non-PNS MPNSTs, and its differential diagnosis is challenging. Canine perivascular wall tumors (PWTs) also commonly arise in soft tissue. Their histopathological features are quite similar to those of canine MPNSTs, making their differential diagnosis challenging. To elucidate whether the morphological features are applicable to diagnose non-PNS MPNSTs and to demonstrate useful markers for distinction between canine MPNSTs and PWTs, the authors examined 30 canine MPNSTs and 31 PWTs immunohistochemically for S100, nestin, NGFR, Olig2, claudin-1, CD57, PRX, α-SMA, desmin, and calponin. Among canine MPNSTs, the PNS tumors displayed significantly higher S100 and Olig2 expression than the non-PNS tumors. The expression levels of the other markers did not differ significantly, suggesting that the same morphological diagnostic criteria are applicable regardless of their location. The PWT cells displayed significantly weaker immunoreactivity than MPNSTs to markers used except α-SMA and desmin. Cluster analysis sorted most canine MPNSTs and PWTs into 2 distinctly different clusters, whereas 3 MPNSTs and 6 PWTs were assigned to the opposing cluster. These 3 MPNSTs were negative for almost all markers, while these 6 PWTs were positive for only neuronal markers. In particular, NGFR and Olig2 were almost negative in the rest of PWT cases. These findings suggest that NGFR and Olig2 are useful to distinguish these 2 tumors.

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Section: Cluster Analysesmentioning

confidence: 60%

The Effects of Tumor Location on Diagnostic Criteria for Canine Malignant Peripheral Nerve Sheath Tumors (MPNSTs) and the Markers for Distinction Between Canine MPNSTs and Canine Perivascular Wall Tumors

2013

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“…Human MPNSTs and MPNST cell lines contain CD133 + cells that may be stem-like cells 138,139 . GEM models of MPNSTs include combined loss of Nf1 and Trp53 (REFS 140,141 ) or Nf1 and Cdkn2a 142,143 .…”

Section: Nf1 Tumorigenesis and Tumour Cells Of Originmentioning

confidence: 99%

A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor

2015

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Neurofibromatosis type 1 (NF1) is a common genetic disorder that predisposes affected individuals to tumours. The NF1 gene encodes a RAS GTPase-activating protein called neurofibromin and is one of several genes that (when mutant) affect RAS–MAPK signalling, causing related diseases collectively known as RASopathies. Several RASopathies, beyond NF1, are cancer predisposition syndromes. Somatic NF1 mutations also occur in 5–10% of human sporadic cancers and may contribute to resistance to therapy. To highlight areas for investigation in RASopathies and sporadic tumours with NF1 mutations, we summarize current knowledge of NF1 disease, the NF1 gene and neurofibromin, neurofibromin signalling pathways and recent developments in NF1 therapeutics.

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“…Upstream molecules in Akt and mitogen-activated protein kinase (MAPK) pathways are preferentially activated in CD133 + colon cancer cells [42]. Ras and its downsteam effectors such as ERK, JNK, PI3K, p38K, and RalA are also significantly activated in CD133 + human primary malignant peripheral nerve sheath tumor [43]. Stemness genes, octamer biding transcription factor 3/4 (OCT4) and/or SRY-box containing gene 2 (SOX2), have been found to bind to the P1 promoter region of CD133 gene loci and ectopic OCT4 or SOX2 expression triggers the CD133P1 activity in the lung cancer cell lines N417, H358, and A549 [44].…”

Section: Introductionmentioning

confidence: 99%

CD133: a stem cell biomarker and beyond

2013

Exp Hematol Oncol

281

190

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Cancer stem cells (CSCs) or tumor initiating cells (TICs) contribute to tumorigenesis, metastasis, recurrence and chemoresistance. CD133, a pentaspan membrane glycoprotein, has been used as a stem cell biomarker for isolation of stem-like cells from a variety of normal and pathological tissues as well as cell lines since its discovery in 1999. Recent studies are focusing on the functionality of CD133. In this review, we summarize new insights into CD133 regulation and the involvement of CD133 in cell self-renewal, tumorigenesis, metastasis, resistance, metabolism, differentiation, autophagy, apoptosis, and regeneration.

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Overactivation of Ras signaling pathway in CD133+ MPNST cells

Cited by 19 publications

References 67 publications

The Effects of Tumor Location on Diagnostic Criteria for Canine Malignant Peripheral Nerve Sheath Tumors (MPNSTs) and the Markers for Distinction Between Canine MPNSTs and Canine Perivascular Wall Tumors

The Effects of Tumor Location on Diagnostic Criteria for Canine Malignant Peripheral Nerve Sheath Tumors (MPNSTs) and the Markers for Distinction Between Canine MPNSTs and Canine Perivascular Wall Tumors

A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor

CD133: a stem cell biomarker and beyond

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