Colony-stimulating factor-1 blockade by antisense oligonucleotides and small interfering RNAs suppresses growth of human mammary tumor xenografts in mice

Seyedhossein Aharinejad, Patrick Paulus, Mouldy Sioud, Michael Hofmann, Karin Zins, Romana Schäfer, E. Richard Stanley, Dietmar Abraham

Research output: Contribution to journalArticle

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Abstract

Colony-stimulating factor (CSF)-1 is the primary regulator of tissue macrophage production. CSF-1 expression is correlated with poor prognosis in breast cancer and is believed to enhance mammary tumor progression and metastasis through the recruitment and regulation of tumor-associated macrophages. Macrophages produce matrix metalloproteases (MMPs) and vascular endothelial growth factor, which are crucial for tumor invasion and angiogenesis. Given the important role of CSF-1, we hypothesized that blockade of CSF-1 or the CSF-1 receptor (the product of the c-fms proto-oncogene) would suppress macrophage infiltration and mammary tumor growth. Human MCF-7 mammary carcinoma cell xenografts in mice were treated with either mouse CSF-1 antisense oligonucleotide for 2 weeks or five intratumoral injections of either CSF-1 small interfering RNAs or c-fms small interfering RNAs. These treatments suppressed mammary tumor growth by 50%, 45%, and 40%, respectively, and selectively down-regulated target protein expression in tumor lysates. Host macrophage infiltration; host MMP-12, MMP-2, and vascular endothelial growth factor A expression; and endothelial cell proliferation within tumors of treated mice were decreased compared with tumors in control mice. In addition, mouse survival significantly increased after CSF-1 blockade. These studies demonstrate that CSF-1 and CSF-1 receptor are potential therapeutic targets for the treatment of mammary cancer.

Original languageEnglish (US)
Pages (from-to)5378-5384
Number of pages7
JournalCancer Research
Volume64
Issue number15
DOIs
StatePublished - Aug 1 2004

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Macrophage Colony-Stimulating Factor
Antisense Oligonucleotides
Heterografts
Small Interfering RNA
Breast Neoplasms
Growth
Macrophages
Metalloproteases
Colony-Stimulating Factor Receptors
Neoplasms
Vascular Endothelial Growth Factor A
fms Genes
Therapeutics
Endothelial Cells
Cell Proliferation
Neoplasm Metastasis
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Colony-stimulating factor-1 blockade by antisense oligonucleotides and small interfering RNAs suppresses growth of human mammary tumor xenografts in mice. / Aharinejad, Seyedhossein; Paulus, Patrick; Sioud, Mouldy; Hofmann, Michael; Zins, Karin; Schäfer, Romana; Stanley, E. Richard; Abraham, Dietmar.

In: Cancer Research, Vol. 64, No. 15, 01.08.2004, p. 5378-5384.

Research output: Contribution to journalArticle

Aharinejad, Seyedhossein ; Paulus, Patrick ; Sioud, Mouldy ; Hofmann, Michael ; Zins, Karin ; Schäfer, Romana ; Stanley, E. Richard ; Abraham, Dietmar. / Colony-stimulating factor-1 blockade by antisense oligonucleotides and small interfering RNAs suppresses growth of human mammary tumor xenografts in mice. In: Cancer Research. 2004 ; Vol. 64, No. 15. pp. 5378-5384.
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