Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis

Chung Ping Liao, Reid C. Booker, Jean Philippe Brosseau, Zhiguo Chen, Juan Mo, Edem Tchegnon, Yong Wang, D. Wade Clapp, Lu Q. Le

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Neurofibromatosis type 1 associates with multiple neoplasms, and the Schwann cell tumor neurofibroma is the most prevalent. A hallmark feature of neurofibroma is mast cell infiltration, which is recruited by chemoattractant stem cell factor (SCF) and has been suggested to sustain neurofibroma tumorigenesis. In the present study, we use new, genetically engineered Scf mice to decipher the contributions of tumor-derived SCF and mast cells to neurofibroma development. We demonstrate that mast cell infiltration is dependent on SCF from tumor Schwann cells. However, removal of mast cells by depleting the main SCF source only slightly affects neurofibroma progression. Other inflammation signatures show that all neurofibromas are associated with high levels of macrophages regardless of Scf status. These findings suggest an active inflammation in neurofibromas and partly explain why mast cell removal alone is not sufficient to relieve tumor burden in this experimental neurofibroma model. Furthermore, we show that plexiform neurofibromas are highly associated with injury-prone spinal nerves that are close to flexible vertebras. In summary, our study details the role of inflammation in neurofibromagenesis. Our data indicate that prevention of inflammation and possibly also nerve injury at the observed tumor locations are therapeutic approaches for neurofibroma prophylaxis and that such treatment should be explored.

Original languageEnglish (US)
Pages (from-to)2848-2861
Number of pages14
JournalJournal of Clinical Investigation
Volume128
Issue number7
DOIs
StatePublished - Jul 2 2018

Fingerprint

Neurofibroma
Tumor Microenvironment
Carcinogenesis
Inflammation
Mast Cells
Stem Cell Factor
Schwann Cells
Neoplasms
Plexiform Neurofibroma
Spinal Nerves
Neurofibromatosis 1
Neoplastic Stem Cells
Chemotactic Factors
Wounds and Injuries
Tumor Burden
Spine
Theoretical Models
Macrophages

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis. / Liao, Chung Ping; Booker, Reid C.; Brosseau, Jean Philippe; Chen, Zhiguo; Mo, Juan; Tchegnon, Edem; Wang, Yong; Clapp, D. Wade; Le, Lu Q.

In: Journal of Clinical Investigation, Vol. 128, No. 7, 02.07.2018, p. 2848-2861.

Research output: Contribution to journalArticle

Liao, CP, Booker, RC, Brosseau, JP, Chen, Z, Mo, J, Tchegnon, E, Wang, Y, Clapp, DW & Le, LQ 2018, 'Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis', Journal of Clinical Investigation, vol. 128, no. 7, pp. 2848-2861. https://doi.org/10.1172/JCI99424
Liao, Chung Ping ; Booker, Reid C. ; Brosseau, Jean Philippe ; Chen, Zhiguo ; Mo, Juan ; Tchegnon, Edem ; Wang, Yong ; Clapp, D. Wade ; Le, Lu Q. / Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis. In: Journal of Clinical Investigation. 2018 ; Vol. 128, No. 7. pp. 2848-2861.
@article{6204842193e64c6988f3ace62dafbc52,
title = "Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis",
abstract = "Neurofibromatosis type 1 associates with multiple neoplasms, and the Schwann cell tumor neurofibroma is the most prevalent. A hallmark feature of neurofibroma is mast cell infiltration, which is recruited by chemoattractant stem cell factor (SCF) and has been suggested to sustain neurofibroma tumorigenesis. In the present study, we use new, genetically engineered Scf mice to decipher the contributions of tumor-derived SCF and mast cells to neurofibroma development. We demonstrate that mast cell infiltration is dependent on SCF from tumor Schwann cells. However, removal of mast cells by depleting the main SCF source only slightly affects neurofibroma progression. Other inflammation signatures show that all neurofibromas are associated with high levels of macrophages regardless of Scf status. These findings suggest an active inflammation in neurofibromas and partly explain why mast cell removal alone is not sufficient to relieve tumor burden in this experimental neurofibroma model. Furthermore, we show that plexiform neurofibromas are highly associated with injury-prone spinal nerves that are close to flexible vertebras. In summary, our study details the role of inflammation in neurofibromagenesis. Our data indicate that prevention of inflammation and possibly also nerve injury at the observed tumor locations are therapeutic approaches for neurofibroma prophylaxis and that such treatment should be explored.",
author = "Liao, {Chung Ping} and Booker, {Reid C.} and Brosseau, {Jean Philippe} and Zhiguo Chen and Juan Mo and Edem Tchegnon and Yong Wang and Clapp, {D. Wade} and Le, {Lu Q.}",
year = "2018",
month = "7",
day = "2",
doi = "10.1172/JCI99424",
language = "English (US)",
volume = "128",
pages = "2848--2861",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "7",

}

TY - JOUR

T1 - Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis

AU - Liao, Chung Ping

AU - Booker, Reid C.

AU - Brosseau, Jean Philippe

AU - Chen, Zhiguo

AU - Mo, Juan

AU - Tchegnon, Edem

AU - Wang, Yong

AU - Clapp, D. Wade

AU - Le, Lu Q.

PY - 2018/7/2

Y1 - 2018/7/2

N2 - Neurofibromatosis type 1 associates with multiple neoplasms, and the Schwann cell tumor neurofibroma is the most prevalent. A hallmark feature of neurofibroma is mast cell infiltration, which is recruited by chemoattractant stem cell factor (SCF) and has been suggested to sustain neurofibroma tumorigenesis. In the present study, we use new, genetically engineered Scf mice to decipher the contributions of tumor-derived SCF and mast cells to neurofibroma development. We demonstrate that mast cell infiltration is dependent on SCF from tumor Schwann cells. However, removal of mast cells by depleting the main SCF source only slightly affects neurofibroma progression. Other inflammation signatures show that all neurofibromas are associated with high levels of macrophages regardless of Scf status. These findings suggest an active inflammation in neurofibromas and partly explain why mast cell removal alone is not sufficient to relieve tumor burden in this experimental neurofibroma model. Furthermore, we show that plexiform neurofibromas are highly associated with injury-prone spinal nerves that are close to flexible vertebras. In summary, our study details the role of inflammation in neurofibromagenesis. Our data indicate that prevention of inflammation and possibly also nerve injury at the observed tumor locations are therapeutic approaches for neurofibroma prophylaxis and that such treatment should be explored.

AB - Neurofibromatosis type 1 associates with multiple neoplasms, and the Schwann cell tumor neurofibroma is the most prevalent. A hallmark feature of neurofibroma is mast cell infiltration, which is recruited by chemoattractant stem cell factor (SCF) and has been suggested to sustain neurofibroma tumorigenesis. In the present study, we use new, genetically engineered Scf mice to decipher the contributions of tumor-derived SCF and mast cells to neurofibroma development. We demonstrate that mast cell infiltration is dependent on SCF from tumor Schwann cells. However, removal of mast cells by depleting the main SCF source only slightly affects neurofibroma progression. Other inflammation signatures show that all neurofibromas are associated with high levels of macrophages regardless of Scf status. These findings suggest an active inflammation in neurofibromas and partly explain why mast cell removal alone is not sufficient to relieve tumor burden in this experimental neurofibroma model. Furthermore, we show that plexiform neurofibromas are highly associated with injury-prone spinal nerves that are close to flexible vertebras. In summary, our study details the role of inflammation in neurofibromagenesis. Our data indicate that prevention of inflammation and possibly also nerve injury at the observed tumor locations are therapeutic approaches for neurofibroma prophylaxis and that such treatment should be explored.

UR - http://www.scopus.com/inward/record.url?scp=85049841082&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049841082&partnerID=8YFLogxK

U2 - 10.1172/JCI99424

DO - 10.1172/JCI99424

M3 - Article

VL - 128

SP - 2848

EP - 2861

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 7

ER -