Clinical & Experimental Metastasis

, Volume 27, Issue 4, pp 233–240

Evaluation of a CXCR4 antagonist in a xenograft mouse model of inflammatory breast cancer

  • Balraj Singh
  • Kendra R. Cook
  • Cecilia Martin
  • Eugene H. Huang
  • Kailash Mosalpuria
  • Savitri Krishnamurthy
  • Massimo Cristofanilli
  • Anthony Lucci
Research Paper

DOI: 10.1007/s10585-010-9321-4

Cite this article as:
Singh, B., Cook, K.R., Martin, C. et al. Clin Exp Metastasis (2010) 27: 233. doi:10.1007/s10585-010-9321-4

Abstract

CXCL12/CXCR4 signaling, being important in the homing of cancer cells to lungs, bone and other organs, is a promising therapeutic target. Our purpose was to determine whether a peptide-based antagonist of CXCR4 would reduce primary tumor growth and/or metastasis in a preclinical mouse model of inflammatory breast cancer. We improved an existing model of inflammatory breast cancer for this study by luciferase transfection of SUM149 cells and the monitoring of such cells in mice by imaging and the luciferase assay. We implanted 2 × 106 SUM49-Luc cells along with matrigel into the left thoracic mammary fat pad of nude mice to produce tumors. Our mouse model exhibited important features of inflammatory breast cancer, namely, aggressive local disease, local metastases and distant metastases. To evaluate the efficacy of a CXCR4 antagonist CTCE-9908, by itself or in combination with paclitaxel, we treated groups of ten mice each with CTCE-9908 (25 mg/kg, injected subcutaneously 5 days/week), control peptide SC-9908, paclitaxel (10 mg/kg, injected subcutaneously twice a week), and CTCE-9908 plus paclitaxel concurrently. We assessed all mice weekly by whole-body luciferase imaging to quantify relative primary tumor burden and distant metastases. At the end of the experiment, we quantified primary tumors by weight and lung metastases by luciferase activity assay on tissue lysates. Paclitaxel, a known chemotherapeutic, inhibited primary tumor growth in our model (P < 0.05). CTCE-9908 did not significantly inhibit primary tumor growth or lung metastases as compared to control groups, without or with paclitaxel (P > 0.05). However, CTCE-9908 as a single therapy inhibited organ-specific metastasis to leg (P < 0.05 by chi-squared test and by two-sample t-test).

Keywords

Inflammatory breast cancerMetastasisCXCR4CXCL12SDF-1Targeted therapyCTCE-9908

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Balraj Singh
    • 1
    • 4
  • Kendra R. Cook
    • 1
  • Cecilia Martin
    • 1
  • Eugene H. Huang
    • 2
  • Kailash Mosalpuria
    • 3
  • Savitri Krishnamurthy
    • 4
    • 5
  • Massimo Cristofanilli
    • 4
    • 6
  • Anthony Lucci
    • 3
    • 4
  1. 1.Department of Surgical Oncology, Unit 107The University of Texas M.D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of Radiation OncologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  3. 3.Department of Surgical Oncology, Unit 444The University of Texas M.D. Anderson Cancer CenterHoustonUSA
  4. 4.Advanced Research Center for Micrometastatic DiseaseThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  5. 5.Department of PathologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  6. 6.Department of Breast Medical OncologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA