A CXCR4 Antagonist CTCE-9908 Inhibits Primary Tumor Growth and Metastasis of Breast Cancer1

Eugene H. Huang, Balraj Singh, Massimo Cristofanilli, Juri Gelovani, Caimiao Wei, Laura Vincent, Kendra R. Cook, Anthony Lucci*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

Background: CXCL12/CXCR4 signaling may be involved in tumor growth and angiogenesis, and homing of cancer cells to bone and other organs. Our purpose was to determine whether inhibition of CXCR4 with a peptide-based antagonist would reduce tumor growth and metastasis of breast cancer. Methods: We used two mouse models of breast cancer. In the first model, 1 × 106 MDA-MB-231 breast cancer cells transfected with luciferase were implanted into the inguinal mammary fat pad to produce primary tumors. In the second model, 1 × 105 MDA-231-BSC12 cells were injected into the left cardiac ventricle to produce bone metastases. CTCE-9908, a peptide analog of CXCL12 that competitively binds to CXCR4, was used to test the effect of inhibiting CXCR4. Five mice from each mouse model were treated with CTCE-9908 (25 mg/kg, injected subcutaneously 5 d/wk). All mice were assessed weekly using bioluminescent imaging to quantify relative volumes of tumor burden. Results: Bioluminescencent imaging showed that the mice treated with CTCE-9908 had significantly less primary tumor burden than the control mice. At 5 and 6 wk, the mice treated with CTCE-9908 had a 7-fold reduction and 5-fold reduction in primary tumor burden, respectively. Treatment with CTCE-9908 also significantly inhibited the rate of metastases compared with the control group. At 5 and 6 wk, the mice treated with CTCE-9908 demonstrated a 9-fold reduction and 20-fold reduction in metastatic tumor burden, respectively. Conclusion: Treatment with the CXCR4 antagonist CTCE-9908 significantly reduced metastasis as well as primary tumor growth in mouse models of breast cancer.

Original languageEnglish (US)
Pages (from-to)231-236
Number of pages6
JournalJournal of Surgical Research
Volume155
Issue number2
DOIs
StatePublished - Aug 1 2009

Keywords

  • CTCE-9908
  • CXCR4
  • SDF-1
  • breast cancer
  • metastasis
  • targeted therapy

ASJC Scopus subject areas

  • Surgery

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