Pathogenesis of plexiform neurofibroma: Tumor-stromal/hematopoietic interactions in tumor progression

Karl Staser, Feng Chun Yang, D. Clapp

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Neurofibromatosis type 1 (NF1) is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1 gene. A second-hit mutation precedes the predominant NF1 neoplasms, which include myeloid leukemia, optic glioma, and plexiform neurofibroma. Despite this requisite NF1 loss of heterozygosity in the tumor cell of origin, nontumorigenic cells contribute to both generalized and specific disease manifestations. In mouse models of plexiform neurofibroma formation, Nf1 haploinsufficient mast cells promote inflammation, accelerating tumor formation and growth. These recruited mast cells, hematopoietic effector cells long known to permeate neurofibroma tissue, mediate key mitogenic signals that contribute to vascular ingrowth, collagen deposition, and tumor growth. Thus, the plexiform neurofibroma microenvironment involves a tumor/stromal interaction with the hematopoietic system that depends, at the molecular level, on a stem cell factor/c-kit-mediated signaling axis. These observations parallel findings in other NF1 disease manifestations and are clearly relevant to medical management of these neurofibromas.

Original languageEnglish
Pages (from-to)469-495
Number of pages27
JournalAnnual Review of Pathology: Mechanisms of Disease
Volume7
DOIs
StatePublished - 2012

Fingerprint

Plexiform Neurofibroma
Neurofibromatosis 1
pathogenesis
neoplasms
mast cells
Neurofibroma
Neoplasms
Mast Cells
stem cell factor
mutation
myeloid leukemia
Neurofibromatosis 1 Genes
Optic Nerve Glioma
permeates
genetic disorders
Hematopoietic System
optics
Mutation
Inborn Genetic Diseases
blood vessels

Keywords

  • C-kit
  • Mast cell
  • Neurofibromatosis
  • NF1
  • SCF

ASJC Scopus subject areas

  • Plant Science

Cite this

Pathogenesis of plexiform neurofibroma : Tumor-stromal/hematopoietic interactions in tumor progression. / Staser, Karl; Yang, Feng Chun; Clapp, D.

In: Annual Review of Pathology: Mechanisms of Disease, Vol. 7, 2012, p. 469-495.

Research output: Contribution to journalArticle

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