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Monitoring Serial Changes in Circulating Human Breast Cancer Cells in Murine Xenograft Models

¹ Breast Oncology Program, Comprehensive Cancer Center, Department of Internal Medicine, ² Department of Radiology, and ³ Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan; and ⁴ Immunicon Corporation, Huntingdon Valley, Pennsylvania

Requests for reprints: Daniel F. Hayes, University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, 6312 Cancer Center, Ann Arbor, MI 48109-0942. Phone: 734-615-6725; Fax: 734-615-3947; E-mail: hayesdf{at}umich.edu or Gary D. Luker, University of Michigan Medical School, 109 Zina Pitcher Place, A526 BSRB, Ann Arbor, MI 48109-2200. Phone: 734-763-5849; Fax: 734-763-5447; E-mail: gluker{at}umich.edu.

Key Words: breast cancer • circulating tumor cells • xenograft

Circulating tumor cells (CTC) are emerging as a powerful prognostic and predictive biomarker in several types of cancer, including breast, colon, and prostate. Studies of CTC in metastasis and further development of CTC as a biomarker in cancer have been limited by the inability to repetitively monitor CTC in mouse models of cancer. We have validated a method to enumerate CTC in blood samples obtained from living mice using a modified version of an in vitro diagnostic system for quantifying CTC in patients. Different routes of blood collection were tested to identify a method to reproducibly recover CTC from tumor-bearing mice without interference from contaminating normal murine epithelial cells. CTC are present in blood samples from mice bearing orthotopic xenografts of several different breast cancer cell lines and primary breast cancer cells from patient biopsies. We also show that this technology can be used for serial monitoring of CTC in mouse xenograft models of human breast cancer. These results establish a new method for studying CTC in mouse models of epithelial cancer, providing the foundation for studies of molecular regulation of CTC in cancer and CTC as biomarker for therapeutic efficacy. [Cancer Res 2008;68(14):5529–32]