Bioluminescent Animal Models of Human Breast Cancer for Tumor Biomass Evaluation and Metastasis Detection

Introduction: Convenient animal models are needed to study the progression and treatment of human tumors in vivo. Luciferase-based bioluminescent imaging (BLI) enables researchers to monitor tumors noninvasively and is sensitive to subtle changes in tumors.

Methods: Three human breast cancer models in nude mice were established by using luciferase-expressing MDA-MB-231-luc cells. They were subcutaneous xenografts (n = 8), mammary gland xenografts (n = 5), and lung metastases (n = 3). The tumors were imaged in live mice by using a highly sensitive BLI system. The relationship between the intensity of bioluminescence from the tumor was analyzed with respect to tumor volume. Bioluminescent signals from lung metastases were studied to determine the threshold of detectability.

Results: Tumors growing in the mice's backs and mammary gland fat pads were imaged dynamically after administration of D-luciferin. The bioluminescent intensity from the tumors gradually increased and then decreased in a one-hour span. The time to reach maximum signal intensity differed significantly among tumors and was independent of tumor volume and unrelated to maximum signal intensity. A significant correlation was observed between tumor volume and maximum signal intensity in tumors from both sites. Lung metastatic lesions of .3-.5 mm in diameter were clearly detectable through the entire animal imaging process.

Conclusion: The animal models established with luciferase-expressing cancer cells in combination with BLI provide a system for rapid, noninvasive, and quantitative analysis of tumor biomass and metastasis. This biosystem simplifies in vivo monitoring of tumors and will be useful for noninvasive investigation of tumor growth and response to therapy.