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

38 Scopus citations

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 - Jan 29 2010

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    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