Stromal cell-derived CSF-1 blockade prolongs xenograft survival of CSF-1-negative neuroblastoma

Dietmar Abraham, Karin Zins, Mouldy Sioud, Trevor Lucas, Romana Schäfer, E. Richard Stanley, Seyedhossein Aharinejad

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The molecular mechanisms of tumor-host interactions that render neuroblastoma (NB) cells highly invasive are unclear. Cancer cells upregulate host stromal cell colony-stimulating factor-1 (CSF-1) production to recruit tumor-associated macrophages (TAMs) and accelerate tumor growth by affecting extracellular matrix remodeling and angiogenesis. By coculturing NB with stromal cells in vitro, we showed the importance of host CSF-1 expression for macrophage recruitment to NB cells. To examine this interaction in NB in vivo, mice bearing human CSF-1-expressing SK-N-AS and CSF-1-negative SK-NDZ NB xenografts were treated with intratumoral injections of small interfering RNAs directed against mouse CSF-1. Significant suppression of both SK-N-AS and SK-N-DZ NB growth by these treatments was associated with decreased TAM infiltration, matrix metalloprotease (MMP)-12 levels and angiogenesis compared to controls, while expression of tissue inhibitors of MMPs increased following mouse CSF-1 blockade. Furthermore, Tie-2-positive and -negative TAMs recruited by host CSF-1 were identified in NB tumor tissue by confocal microscopy and flow cytometry. However, host-CSF-1 blockade prolonged survival only in CSF-1-negative SK-N-DZ NB. These studies demonstrated that increased CSF-1 production by host cells enhances TAM recruitment and NB growth and that the CSF-1 phenotype of NB tumor cells adversely affects survival.

Original languageEnglish (US)
Pages (from-to)1339-1352
Number of pages14
JournalInternational Journal of Cancer
Volume126
Issue number6
DOIs
StatePublished - 2010

Fingerprint

Macrophage Colony-Stimulating Factor
Stromal Cells
Neuroblastoma
Heterografts
Neoplasms
Macrophages
Growth
Matrix Metalloproteinase Inhibitors
Survival
Metalloproteases
Confocal Microscopy
Small Interfering RNA
Extracellular Matrix
Flow Cytometry
Up-Regulation
Phenotype

Keywords

  • Growth factors and receptors
  • Neuroblastoma
  • Tumor-stromal cell interactions
  • Xenograft models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Abraham, D., Zins, K., Sioud, M., Lucas, T., Schäfer, R., Stanley, E. R., & Aharinejad, S. (2010). Stromal cell-derived CSF-1 blockade prolongs xenograft survival of CSF-1-negative neuroblastoma. International Journal of Cancer, 126(6), 1339-1352. https://doi.org/10.1002/ijc.24859

Stromal cell-derived CSF-1 blockade prolongs xenograft survival of CSF-1-negative neuroblastoma. / Abraham, Dietmar; Zins, Karin; Sioud, Mouldy; Lucas, Trevor; Schäfer, Romana; Stanley, E. Richard; Aharinejad, Seyedhossein.

In: International Journal of Cancer, Vol. 126, No. 6, 2010, p. 1339-1352.

Research output: Contribution to journalArticle

Abraham, D, Zins, K, Sioud, M, Lucas, T, Schäfer, R, Stanley, ER & Aharinejad, S 2010, 'Stromal cell-derived CSF-1 blockade prolongs xenograft survival of CSF-1-negative neuroblastoma', International Journal of Cancer, vol. 126, no. 6, pp. 1339-1352. https://doi.org/10.1002/ijc.24859
Abraham, Dietmar ; Zins, Karin ; Sioud, Mouldy ; Lucas, Trevor ; Schäfer, Romana ; Stanley, E. Richard ; Aharinejad, Seyedhossein. / Stromal cell-derived CSF-1 blockade prolongs xenograft survival of CSF-1-negative neuroblastoma. In: International Journal of Cancer. 2010 ; Vol. 126, No. 6. pp. 1339-1352.
@article{0734be80118543c5b11ce0f882fa85fc,
title = "Stromal cell-derived CSF-1 blockade prolongs xenograft survival of CSF-1-negative neuroblastoma",
abstract = "The molecular mechanisms of tumor-host interactions that render neuroblastoma (NB) cells highly invasive are unclear. Cancer cells upregulate host stromal cell colony-stimulating factor-1 (CSF-1) production to recruit tumor-associated macrophages (TAMs) and accelerate tumor growth by affecting extracellular matrix remodeling and angiogenesis. By coculturing NB with stromal cells in vitro, we showed the importance of host CSF-1 expression for macrophage recruitment to NB cells. To examine this interaction in NB in vivo, mice bearing human CSF-1-expressing SK-N-AS and CSF-1-negative SK-NDZ NB xenografts were treated with intratumoral injections of small interfering RNAs directed against mouse CSF-1. Significant suppression of both SK-N-AS and SK-N-DZ NB growth by these treatments was associated with decreased TAM infiltration, matrix metalloprotease (MMP)-12 levels and angiogenesis compared to controls, while expression of tissue inhibitors of MMPs increased following mouse CSF-1 blockade. Furthermore, Tie-2-positive and -negative TAMs recruited by host CSF-1 were identified in NB tumor tissue by confocal microscopy and flow cytometry. However, host-CSF-1 blockade prolonged survival only in CSF-1-negative SK-N-DZ NB. These studies demonstrated that increased CSF-1 production by host cells enhances TAM recruitment and NB growth and that the CSF-1 phenotype of NB tumor cells adversely affects survival.",
keywords = "Growth factors and receptors, Neuroblastoma, Tumor-stromal cell interactions, Xenograft models",
author = "Dietmar Abraham and Karin Zins and Mouldy Sioud and Trevor Lucas and Romana Sch{\"a}fer and Stanley, {E. Richard} and Seyedhossein Aharinejad",
year = "2010",
doi = "10.1002/ijc.24859",
language = "English (US)",
volume = "126",
pages = "1339--1352",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Stromal cell-derived CSF-1 blockade prolongs xenograft survival of CSF-1-negative neuroblastoma

AU - Abraham, Dietmar

AU - Zins, Karin

AU - Sioud, Mouldy

AU - Lucas, Trevor

AU - Schäfer, Romana

AU - Stanley, E. Richard

AU - Aharinejad, Seyedhossein

PY - 2010

Y1 - 2010

N2 - The molecular mechanisms of tumor-host interactions that render neuroblastoma (NB) cells highly invasive are unclear. Cancer cells upregulate host stromal cell colony-stimulating factor-1 (CSF-1) production to recruit tumor-associated macrophages (TAMs) and accelerate tumor growth by affecting extracellular matrix remodeling and angiogenesis. By coculturing NB with stromal cells in vitro, we showed the importance of host CSF-1 expression for macrophage recruitment to NB cells. To examine this interaction in NB in vivo, mice bearing human CSF-1-expressing SK-N-AS and CSF-1-negative SK-NDZ NB xenografts were treated with intratumoral injections of small interfering RNAs directed against mouse CSF-1. Significant suppression of both SK-N-AS and SK-N-DZ NB growth by these treatments was associated with decreased TAM infiltration, matrix metalloprotease (MMP)-12 levels and angiogenesis compared to controls, while expression of tissue inhibitors of MMPs increased following mouse CSF-1 blockade. Furthermore, Tie-2-positive and -negative TAMs recruited by host CSF-1 were identified in NB tumor tissue by confocal microscopy and flow cytometry. However, host-CSF-1 blockade prolonged survival only in CSF-1-negative SK-N-DZ NB. These studies demonstrated that increased CSF-1 production by host cells enhances TAM recruitment and NB growth and that the CSF-1 phenotype of NB tumor cells adversely affects survival.

AB - The molecular mechanisms of tumor-host interactions that render neuroblastoma (NB) cells highly invasive are unclear. Cancer cells upregulate host stromal cell colony-stimulating factor-1 (CSF-1) production to recruit tumor-associated macrophages (TAMs) and accelerate tumor growth by affecting extracellular matrix remodeling and angiogenesis. By coculturing NB with stromal cells in vitro, we showed the importance of host CSF-1 expression for macrophage recruitment to NB cells. To examine this interaction in NB in vivo, mice bearing human CSF-1-expressing SK-N-AS and CSF-1-negative SK-NDZ NB xenografts were treated with intratumoral injections of small interfering RNAs directed against mouse CSF-1. Significant suppression of both SK-N-AS and SK-N-DZ NB growth by these treatments was associated with decreased TAM infiltration, matrix metalloprotease (MMP)-12 levels and angiogenesis compared to controls, while expression of tissue inhibitors of MMPs increased following mouse CSF-1 blockade. Furthermore, Tie-2-positive and -negative TAMs recruited by host CSF-1 were identified in NB tumor tissue by confocal microscopy and flow cytometry. However, host-CSF-1 blockade prolonged survival only in CSF-1-negative SK-N-DZ NB. These studies demonstrated that increased CSF-1 production by host cells enhances TAM recruitment and NB growth and that the CSF-1 phenotype of NB tumor cells adversely affects survival.

KW - Growth factors and receptors

KW - Neuroblastoma

KW - Tumor-stromal cell interactions

KW - Xenograft models

UR - http://www.scopus.com/inward/record.url?scp=74949090694&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=74949090694&partnerID=8YFLogxK

U2 - 10.1002/ijc.24859

DO - 10.1002/ijc.24859

M3 - Article

VL - 126

SP - 1339

EP - 1352

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 6

ER -