Autocrine inhibition of the c-fms proto-oncogene reduces breast cancer bone metastasis assessed with in vivo dual-modality imaging

Justin J. Jeffery, Katie Lux, John S. Vogel, Wynetta D. Herrera, Stephen Greco, Ho Hyung Woo, Nisreen AbuShahin, Mark D. Pagel, Setsuko K. Chambers

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Breast cancer cells preferentially home to the bone microenvironment, which provides a unique niche with a network of multiple bidirectional communications between host and tumor, promoting survival and growth of bone metastases. In the bone microenvironment, the c-fms proto-oncogene that encodes for the CSF-1 receptor, along with CSF-1, serves as one critical cytokine/receptor pair, functioning in paracrine and autocrine fashion. Previous studies concentrated on the effect of inhibition of host (mouse) c-fms on bone metastasis, with resulting decrease in osteolysis and bone metastases as a paracrine effect. In this report, we assessed the role of c-fms inhibition within the tumor cells (autocrine effect) in the early establishment of breast cancer cells in bone and the effects of this early c-fms inhibition on subsequent bone metastases and destruction. This study exploited a multidisciplinary approach by employing two non-invasive, in vivo imaging methods to assess the progression of bone metastases and bone destruction, in addition to ex vivo analyses using RT-PCR and histopathology. Using a mouse model of bone homing human breast cancer cells, we showed that an early one-time application of anti-human c-fms antibody delayed growth of bone metastases and bone destruction for at least 31 days as quantitatively measured by bioluminescence imaging and computed tomography, compared to controls. Thus, neutralizing human c-fms in the breast cancer cell alone decreases extent of subsequent bone metastasis formation and osteolysis. Furthermore, we are the first to show that anti-c-fms antibodies can impact early establishment of breast cancer cells in bone.

Original languageEnglish (US)
Pages (from-to)404-413
Number of pages10
JournalExperimental Biology and Medicine
Volume239
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • C-fms proto-oncogene
  • autocrine
  • bone metastasis
  • breast cancer
  • osteolysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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