Research Paper

Clinical & Experimental Metastasis

, Volume 27, Issue 4, pp 233-240

First online:

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

  • Balraj SinghAffiliated withDepartment of Surgical Oncology, Unit 107, The University of Texas M.D. Anderson Cancer CenterAdvanced Research Center for Micrometastatic Disease, The University of Texas M.D. Anderson Cancer Center
  • , Kendra R. CookAffiliated withDepartment of Surgical Oncology, Unit 107, The University of Texas M.D. Anderson Cancer Center
  • , Cecilia MartinAffiliated withDepartment of Surgical Oncology, Unit 107, The University of Texas M.D. Anderson Cancer Center
  • , Eugene H. HuangAffiliated withDepartment of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center
  • , Kailash MosalpuriaAffiliated withDepartment of Surgical Oncology, Unit 444, The University of Texas M.D. Anderson Cancer Center
  • , Savitri KrishnamurthyAffiliated withAdvanced Research Center for Micrometastatic Disease, The University of Texas M.D. Anderson Cancer CenterDepartment of Pathology, The University of Texas M.D. Anderson Cancer Center
  • , Massimo CristofanilliAffiliated withAdvanced Research Center for Micrometastatic Disease, The University of Texas M.D. Anderson Cancer CenterDepartment of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center
  • , Anthony LucciAffiliated withDepartment of Surgical Oncology, Unit 444, The University of Texas M.D. Anderson Cancer CenterAdvanced Research Center for Micrometastatic Disease, The University of Texas M.D. Anderson Cancer Center Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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 cancer Metastasis CXCR4 CXCL12 SDF-1 Targeted therapy CTCE-9908