Targeting αv-integrins decreased metastasis and increased survival in a nude rat breast cancer brain metastasis model

Y. Jeffrey Wu, Leslie L. Muldoon, Seymur Gahramanov, Dale F. Kraemer, Deborah J. Marshall, Edward A. Neuwelt

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Brain metastases commonly occur in patients with breast, lung and melanoma systemic cancers. The anti-αV integrin monoclonal antibody intetumumab binds cell surface proteins important for adhesion, invasion and angiogenesis in the metastatic cascade. The objective of this study was to investigate the anti-metastatic effect of intetumumab in a hematogenous breast cancer brain metastasis model. Female nude rats received intra-carotid infusion of human brain-seeking metastatic breast cancer cells (231BR-HER2) and were randomly assigned into four groups: (1) control; (2) intetumumab mixed with cells in vitro 5 min before infusion without further treatment; (3) intetumumab intravenously 4 h before and weekly after cell infusion; (4) intetumumab intravenously weekly starting 7 days after cell infusion. Brain metastases were detected by magnetic resonance imaging (MRI) and immunohistochemistry. Comparisons were made using the Kruskal-Wallis test and Dunnett's test. Survival times were estimated using Kaplan-Meier analysis. All control rats with brain tissue available for histology (9 of 11 rats) developed multiple brain metastases (median = 14). Intetumumab treatment either in vitro prior to cell infusion or intravenous before or after cell infusion prevented metastasis formation on MRI and decreased the number of metastases on histology (median = 2, p = 0.0055), including 30 % of animals without detectable tumors at the end of the study. The overall survival was improved by intetumumab compared to controls (median 77+ vs. 52 days, p = 0.0277). Our results suggest that breast cancer patients at risk of metastases might benefit from early intetumumab treatment.

Original languageEnglish (US)
Pages (from-to)27-36
Number of pages10
JournalJournal of Neuro-Oncology
Volume110
Issue number1
DOIs
StatePublished - Oct 2012

Keywords

  • Brain metastasis
  • Breast cancer
  • Integrin
  • Intetumumab
  • MRI

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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