Abstract
Circulating tumor cells (CTCs) have been detected in the bloodstream of both early-stage and advanced cancer patients. However, very little is know about the dynamics of CTCs during cancer progression and the clinical relevance of longitudinal CTC enumeration. To address this, we developed a simple bioluminescence imaging assay to detect CTCs in mouse models of metastasis. In a 4T1 orthotopic metastatic mammary carcinoma mouse model, we demonstrated that this quantitative method offers sensitivity down to 2 CTCs in 0.1–1mL blood samples and high specificity for CTCs originating from the primary tumor, independently of their epithelial status. In this model, we simultaneously monitored blood CTC dynamics, primary tumor growth, and lung metastasis progression over the course of 24 days. Early in tumor development, we observed low numbers of CTCs in blood samples (10–15 cells/100 µL) and demonstrated that CTC dynamics correlate with viable primary tumor growth. To our knowledge, these data represent the first reported use of bioluminescence imaging to detect CTCs and quantify their dynamics in any cancer mouse model. This new assay is opening the door to the study of CTC dynamics in a variety of animal models. These studies may inform clinical decision on the appropriate timing of blood sampling and value of longitudinal CTC enumeration in cancer patients.
Highlights
The invasion of circulating tumor cells (CTCs) into blood represents a critical step in the process of cancer metastasis, which is responsible for 90% of cancer deaths
Using the linear correlation established between background-corrected Bioluminescence imaging (BLI) signals and number of CTCs, we showed that this improved method can be used to quantify as few as 2 CTCs in a 100-ul spiked mouse blood sample (Fig. S3C)
We developed a method using bioluminescence imaging to detect and quantify low numbers of GL-expressing CTCs in mouse blood samples in a living mouse model of metastatic breast cancer
Summary
The invasion of circulating tumor cells (CTCs) into blood represents a critical step in the process of cancer metastasis, which is responsible for 90% of cancer deaths. Many exciting technologies have been developed in the past decade to detect CTCs in patient blood samples [3]. These techniques can enrich and detect CTCs in human blood based on their physical properties, such as filtering them by size, and/or their biological properties, such as protein expression, using immunocytochemistry or multi-marker RT-PCR [1,3]. CTCs can be detected and captured on various platforms, including microfluidic chips, immunomagnetic beads, immunomagnetic columns and membrane filter devices [1]. These CTC platforms may enable a broad range of novel clinical applications, from the early detection of metastatic disease to the prediction of therapeutic response
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
