title: Autocrine inhibition of the c-fms proto-oncogene reduces breast cancer bone metastasis assessed with in vivo dual-modality imaging.
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.
authors.affiliation: Department of Biomedical Engineering, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Jeffery
authors.forename: Katie
authors.initials: K
authors.lastname: Lux
authors.forename: John S
authors.initials: JS
authors.lastname: Vogel
authors.forename: Wynetta D
authors.initials: WD
authors.lastname: Herrera
authors.forename: Stephen
authors.initials: S
authors.lastname: Greco
authors.forename: Ho-Hyung
authors.initials: HH
authors.lastname: Woo
authors.forename: Nisreen
authors.initials: N
authors.lastname: AbuShahin
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pagel
authors.forename: Setsuko K
authors.initials: SK
authors.lastname: Chambers
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D016236:Genes, fms / Q000502:physiology*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010014:Osteolysis / Q000235:genetics; D000090063:Proto-Oncogene Mas; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D059016:Tumor Microenvironment
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: C-fms proto-oncogene; autocrine; bone metastasis; breast cancer; osteolysis