| Autor: |
Dan R. Laks, Daochun Sun, Swathi V. Iyer, Xiyuan Zhang, Sameer Farouk-Sait, Luis F. Parada, Xuanhua Xie, Zilai Wang, Rebecca Brown, John F. Shern, Yu-Jung Chen, Mollie E. Chipman |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| DOI: |
10.2139/ssrn.3732377 |
| Popis: |
NF1-associated malignant peripheral nerve sheath tumors (MPNST) are the major cause of mortality in neurofibromatosis. MPNST arise from benign peripheral nerve plexiform neurofibromas (PN) which originate in the embryonic neural crest cell lineage. Here we employ reporter transgenes that label early neural crest lineage cells in multiple NF1 MPNST mouse models to discover and characterize a rare MPNST cell population with stem cell-like properties including quiescence that is essential for tumor initiation and relapse. Following isolation of these cells we derive a cancer stem cell specific gene expression signature that includes consensus embryonic neural crest genes and also identify Nestin as a novel marker for the MPNST cell of origin. Combined targeting of cancer stem cells together with antimitotic chemotherapy yields effective tumor inhibition and prolongs survival. Finally, application of the mouse cancer stem cell signature to single cell sequencing data from a rare NF1-associated patient MPNST precursor tumor, identifies preformed unsupervised gene expression cell clusters. Enrichment of the cancer stem cell signature in cognate human tumors supports the generality and relevance of cancer stem cells to MPNST therapy development. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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