EMT-independent detection of circulating tumor cells in human blood samples and pre-clinical mouse models of metastasis

Circulating tumor cells (CTCs) present an opportunity to detect/monitor metastasis throughout disease progression. The CellSearch (R) is currently the only FDA-approved technology for CTC detection in patients. The main limitation of this system is its reliance on epithelial markers for CTC isolation/enumeration, which reduces its ability to detect more aggressive mesenchymal CTCs that are generated during metastasis via epithelial-to-mesenchymal transition (EMT). This Technical Note describes and validates two EMT-independent CTC analysis protocols; one for human samples using Parsortix (R) and one for mouse samples using VyCap. Parsortix (R) identifies significantly more mesenchymal human CTCs compared to the clinical CellSearch (R) test, and VyCap identifies significantly more CTCs compared to our mouse CellSearch (R) protocol regardless of EMT status. Recovery and downstream molecular characterization of CTCs is highly feasible using both Parsortix (R) and VyCap. The described CTC protocols can be used by investigators to study CTC generation, EMT and metastasis in both pre-clinical models and clinical samples.

Automated summary

Circulating tumor cells (CTCs) provide an opportunity to detect and monitor metastatic cancer, with different technologies allowing for better analysis and identification of CTCs, offering new insights into the study of metastasis and circulating tumor cells.