Abstract
Circulating tumor cells (CTCs) are promising tools for risk prediction and the monitoring of response to therapy in cancer patients. Within the EU/IMI CANCER-ID consortium, we validated CTC enrichment systems for future inclusion into clinical trials. Due to the known heterogeneity of markers expressed on CTCs, we tested the Parsortix® system (ANGLE plc) which enables label-independent CTC enrichment from whole blood based on increased size and deformability of these tumor cells compared to leukocytes. We performed extensive comparisons both with spiked-in blood models (i.e., MDA-MB-468 tumor cell line cells spiked at very low concentration into blood from healthy donors) and validated the protocol on actual clinical samples from breast, lung, and gastrointestinal cancer patients to define optimal conditions for CTC enrichment. Multiple parameters including cassette gap, separation pressure, and cell fixatives were compared in parallel. Also, the compatibility of blood collection tubes with whole genome amplification of isolated tumor cells was demonstrated and we furthermore established a workflow for semi-automated CTC detection using a quantitative cell imager. The established workflow will contribute to supporting the use of size-based CTC enrichment platforms in clinical trials testing the clinical validity and utility of CTCs for personalized medicine.
Highlights
Solid tumors are able to actively or passively shed tumor cells into the blood at times as early as primary tumor formation [1]
We focused on Circulating tumor cells (CTCs) capture rates for the different cassette gap sizes (6.5 μm and 10 μm), in 3 different blood sample types (EDTA, Ficoll, and CellSave® ) and two separation pressures (23 mbar and 99 mbar) to allow a comprehensive overview (Table 1)
Healthy donor (HD) blood collected in EDTA or CellSave®
Summary
Solid tumors are able to actively or passively shed tumor cells into the blood at times as early as primary tumor formation [1]. A subset of these circulating tumor cells (CTCs) harbors the potential to extravasate from the circulation and colonize distant organs. CTCs have been shown to correlate significantly with the probability of metastatic relapse in various carcinomas [2]. These studies demonstrate that the capability of a tumor to release malignant cells into the blood presents a specific risk for the development of metastasis. In addition to CTC enumeration, the characterization of these rare cells holds great promise as they harbor valuable information on the patient’s current tumor profile and could function as “liquid biopsy” [3,4]
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