The Plexiform Neurofibroma Microenvironment

Feng Chun Yang, Karl Staser, D. Clapp

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Dynamic interactions between tumorigenic cells and surrounding cells, including immunomodulatory hematopoietic cells, can dictate tumor initiation, progression, and transformation. Hematopoietic-stromal interactions underpin the plexiform neurofibroma, a debilitating tumor arising in individuals afflicted with Neurofibromatosis type 1 (NF1), a common genetic disorder resulting from mutations in the NF1 tumor suppressor gene. At the tissue level, plexiform neurofibromas demonstrate a complex microenvironment composed of Schwann cells, fibroblasts, perineural cells, mast cells, secreted collagen, and blood vessels. At the cellular level, specific interactions between these cells engender tumor initiation and progression. In this microenvironment hypothesis, tumorigenic Schwann cells secrete pathological concentrations of stem cell factor, which recruit c-kit expressing mast cells. In turn, activated mast cells release inflammatory effectors stimulating the tumorigenic Schwann cells and their supporting fibroblasts and blood vessels, thus promoting tumor expansion in a feed-forward loop. Bone marrow transplantation experiments in plexiform neurofibroma mouse models have shown that tumorigenesis requires Nf1 haploinsufficiency in the hematopoietic compartment, suggesting that tumor microenvironments can depend on intricate interactions at both cellular and genetic levels. Overall, our continued understanding of critical tumor-stromal interactions will illuminate novel therapeutic targets, as shown by the first-ever successful medical treatment of a plexiform neurofibroma by targeted inhibition of the stem cell factor/c-kit axis.

Original languageEnglish
Pages (from-to)1-4
Number of pages4
JournalCancer Microenvironment
DOIs
StateAccepted/In press - 2012

Fingerprint

Plexiform Neurofibroma
Schwann Cells
Mast Cells
Neurofibromatosis 1
Stem Cell Factor
Neoplasms
Blood Vessels
Fibroblasts
Haploinsufficiency
Inborn Genetic Diseases
Tumor Microenvironment
Tumor Suppressor Genes
Bone Marrow Transplantation
Cell Communication
Carcinogenesis
Collagen
Mutation
Therapeutics

Keywords

  • Mast cells
  • Neurofibromas
  • NF1
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The Plexiform Neurofibroma Microenvironment. / Yang, Feng Chun; Staser, Karl; Clapp, D.

In: Cancer Microenvironment, 2012, p. 1-4.

Research output: Contribution to journalArticle

Yang, Feng Chun ; Staser, Karl ; Clapp, D. / The Plexiform Neurofibroma Microenvironment. In: Cancer Microenvironment. 2012 ; pp. 1-4.
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