Stem cell origin and microenvironment contribution for NF1-associated neurofibromas

L. Q. Le, T. Shipman, D. K. Burns, L. F. Parada

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The tumor predisposition disorder Neurofibromatosis type I (NF1) is one of the most common genetic disorders of the nervous system. It is caused by mutation in the Nf1 tumor suppressor gene, which encodes a GTPase Activating Protein (GAP) that negatively regulates p21-RAS. The development of malignant nerve tumors and neurofibromas, the most frequent tumors in NF1, is a serious complication of the disease. However, little is known about the molecular mechanisms mediating the initiation and progression of these complex tumors, as well as the identity of the specific cell type that gives rise to dermal or cutaneous neurofibromas. In this study, we identify a population of neural crest related stem cells residing in the dermis termed Skin Derived Precursors (SKPs) that, through loss of Nf1, form neurofibromas. We propose that SKPs, or their derivatives, are the cell of origin of dermal neurofibroma. We also provide evidence that additional signals from the non-neoplastic cells in the tumor microenvironment play essential roles in neurofibroma tumorigenesis. These new findings provide a novel approach to gain a greater understanding of the molecular pathogenesis of neurofibroma and exploit innovative therapeutic approach in clinical trial to treat NF1-associated neurofibromas.

Original languageEnglish (US)
Title of host publicationThe Third International Conference on the Development of Biomedical Engineering in Vietnam
Pages219-222
Number of pages4
DOIs
StatePublished - May 21 2010
Event3rd International Conference on the Development of Biomedical Engineering in Vietnam - Ho Chi Minh City, Viet Nam
Duration: Jan 11 2010Jan 14 2010

Publication series

NameIFMBE Proceedings
Volume27
ISSN (Print)1680-0737

Other

Other3rd International Conference on the Development of Biomedical Engineering in Vietnam
CountryViet Nam
CityHo Chi Minh City
Period1/11/101/14/10

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Keywords

  • Dermal neurofibroma
  • NF1
  • Neurofibromin
  • SKPs
  • Tumor microenvironment

ASJC Scopus subject areas

  • Bioengineering
  • Biomedical Engineering

Cite this

Le, L. Q., Shipman, T., Burns, D. K., & Parada, L. F. (2010). Stem cell origin and microenvironment contribution for NF1-associated neurofibromas. In The Third International Conference on the Development of Biomedical Engineering in Vietnam (pp. 219-222). (IFMBE Proceedings; Vol. 27). https://doi.org/10.1007/978-3-642-12020-6-55