Stem-like cells drive NF1-associated MPNST functional heterogeneity and tumor progression. Cell Stem Cell 2021 Aug 05;28(8):1397-1410.e4
Date
05/20/2021Pubmed ID
34010628Pubmed Central ID
PMC8349880DOI
10.1016/j.stem.2021.04.029Scopus ID
2-s2.0-85107299241 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
NF1-associated malignant peripheral nerve sheath tumors (MPNSTs) are the major cause of mortality in neurofibromatosis. MPNSTs arise from benign peripheral nerve plexiform neurofibromas that originate in the embryonic neural crest cell lineage. Using reporter transgenes that label early neural crest lineage cells in multiple NF1 MPNST mouse models, we 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 identify Nestin as a marker for the MPNST cell of origin. Combined targeting of cancer stem cells along with antimitotic chemotherapy yields effective tumor inhibition and prolongs survival. Enrichment of the cancer stem cell signature in cognate human tumors supports the generality and relevance of cancer stem cells to MPNST therapy development.
Author List
Sun D, Xie XP, Zhang X, Wang Z, Sait SF, Iyer SV, Chen YJ, Brown R, Laks DR, Chipman ME, Shern JF, Parada LFAuthor
Daochun Sun PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDisease Models, Animal
Mice
Neoplasm Recurrence, Local
Neurofibromatosis 1
Neurofibrosarcoma
