K. Morris, C. Bilynsky, A.-L. Papa
The George Washington University,
Keywords: cancer, metastasis, platelets
Summary:Circulating tumor cells (CTCs) are a potential biomarker of patient progression and can be detected in patients who have no known cancer metastasis, or patients who have early-stage cancer. Deriving from primary tumors or metastatic sites, CTCs can be very valuable for diagnosis, prognosis, and patient monitoring (Ge et al., 2020). Although their primary function is to maintain hemostasis, platelets are known to have an important role in supporting metastasis by increasing CTC survival while in circulation. They essentially guard CTCs and promote dissemination by protecting them from immune elimination and encouraging CTC arrest within the vasculature (Gay & Felding-Habermann, 2011). The CellSearch system is the first and only FDA approved technique for CTC detection and enumeration. However, it relies on the detection of cell surface epithelial cell adhesion marker, EpCAM (Xiang et al., 2020), making the selection exclusive to cells expressing this phenotype. Cancer cells that have undergone epithelial to mesenchymal transition (EMT) have reduced or no EpCAM expression. Therefore, we describe a system that is not antibody-based, but rather takes advantage of the natural platelet-cancer cell interaction to capture CTCs. Our system is theoretically applicable for the detection of all phenotypes, including cells of the more aggressive, mesenchymal phenotype. Our approach begins by first engineering magnetic probes using modified platelets (Papa et al., 2019), and magnetic nanoparticles (Fig. 1). Next, the magnetic probes interact with cancer cells present in blood followed by the magnetic retrieval of the cancer cells. This approach has allowed the consistent retrieval and isolation of human breast cancer cells of the mesenchymal-like phenotype, MDA-MB-231, in spiked blood samples. Our approach has shown a retrieval rate of 71.2% 12.6%, events including both single cancer cells and clusters of cancer cells with MDA-MB-231 (Fig. 2). Thus, the actual retrieval of MDA-MB-231 is at least 71.2%. We will present a thorough and detailed analysis of single cells and clusters’ retrieval using multiple cancer cells lines to assess the technology for various cancer origins and cancer cell phenotypes. This will include cluster profiling in terms of CTC count distribution within these clusters. A future clinical application of our proposed system is that CTCs retrieved from a patient’s blood specimen can be characterized further in order to assist in patient monitoring for emerging resistance, as well as personalized cancer therapy based on CTC profile.