Colony-stimulating factor-1 antibody reverses chemoresistance in human MCF-7 breast cancer xenografts

Patrick Paulus, E. Richard Stanley, Romana Schäfer, Dietmar Abraham, Seyedhossein Aharinejad

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149 Scopus citations

Abstract

Overexpression of colony-stimulating factor-1 (CSF-1) and its receptor in breast cancer is correlated with poor prognosis. Based on the hypothesis that blockade of CSF-1 would be beneficial in breast cancer treatment, we developed a murinized, polyethylene glycol-linked antigen-binding fragment (Fab) against mouse (host) CSF-1 (anti-CSF-1 Fab). Mice bearing human, chemoresistant MCF-7 breast cancer xenografts were treated with combination chemotherapy (CMF: cyclophosphamide, methotrexate, 5-fluorouracil; cycled twice i.p.), anti-CSF-1 Fab (i.p., cycled every 3 days for 14 days), combined CMF and anti-CSF-1 Fab, or with Ringer's solution as a control. Anti-CSF-1 Fab alone suppressed tissue CSF-1 and retarded tumor growth by 40%. Importantly, in combination with CMF, anti-CSF-1 Fab reversed chemoresistance of MCF-7 xenografts, suppressing tumor development by 56%, down-regulating expression of the chemoresistance genes breast cancer-related protein, multidrug resistance gene 1, and glucosylceramide synthase, and prolonging survival significantly. Combined treatment also reduced angiogenesis and macrophage recruitment and down-regulated tumor matrix metalloproteinase-2 (MMP-2) and MMP-12 expression. These studies support the paradigm of CSF-1 blockade in the treatment of solid tumors and show that: anti-CSF-1 antibodies are potential therapeutic agents for the treatment of mammary cancer.

Original languageEnglish (US)
Pages (from-to)4349-4356
Number of pages8
JournalCancer Research
Volume66
Issue number8
DOIs
Publication statusPublished - Apr 15 2006

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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