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

作者：Huang Eugene H; Singh Balraj; Cristofanilli Massimo; Gelovani Juri; Wei Caimiao; Vincent Laura; Cook Kendra R; Lucci Anthony^*

来源：Journal of Surgical Research, 2009, 155(2): 231-236.

DOI：10.1016/j.jss.2008.06.044

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

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 x 10(6) 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 x 10(5) 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.

• 出版日期2009-8