Capture of mesothelioma cells with ‘universal’ CTC-chip

Abstract

Abstract. Malignant mesothelioma (MM) is a highly aggressive malignant tumor, predominantly associated with job-related exposure to asbestos. Development of effective and non-invasive modalities for diagnosis is an important issue in occupational medicine. Circulating tumor cells (CTCs), which are tumor cells that are shed from primary tumors and circulate in the peripheral blood, may be detected at an earlier stage than malignant tumors, and detection of CTCs may provide a novel insight into the diagnosis of MM. In a previous study evaluating clinical utility of CTCs, detected with a widely used system 'CellSearch', the authors indicated a significant however insufficient capability in the diagnosis of MM, suggesting need for a more sensitive system. Accordingly, the authors developed a novel microfluidic system to capture CTCs (CTC-chip), and demonstrated that the CTC-chip effectively captured MM cells (ACC-MESO-4) spiked in the blood by conjugating an anti-podoplanin antibody. The results of the present study demonstrated that the CTC-chip coated with the anti-podoplanin antibody captured another MM cell (ACC-MESO-1). However, the capture efficiencies were lower than those for ACC-MESO-4. In addition, an anti-mesothelin antibody was used to capture CTCs, however the CTC-chip coated with the anti-mesothelin antibody failed to effectively capture MM cells, possibly due to low mesothelin expression. Overall, the CTC-chip may capture specific types of CTCs by conjugating any antibody against an antigen expressed on CTCs, and may be a useful system for the diagnosis of malignant tumors, including MM.

Detection of circulating tumor cells with a novel microfluidic system in malignant pleural mesothelioma

“…The actual number of cells that were sent into the chip (N‐total) was determined by counting the number of cells that passed through the inlet of the CTC‐chip, and the number of captured cells (N‐captured) was also determined by counting CFSE‐labelled cells remained on the CTC‐chip. The cell capture efficiency was represented as N‐captured/N‐total . Experiments were carried out in triplicate.…”

“…The cell capture efficiency was represented as N-captured/N-total. [12][13][14] Experiments were carried out in triplicate. Circulating tumor cells were quantitatively evaluated as described previously.…”

“…The most important advantage of the novel CTC‐chip system is its capability of conjugating any Ab to capture CTCs (“universal” CTC‐chip), which could enable capture of a wide variety of CTCs by conjugating appropriate Abs. In fact, our previous experimental studies showed that MPM tumor cells were captured with the CTC‐chip coated with an Ab against podoplanin that was abundantly expressed on mesothelial cells . However, the capture efficacy of tumor cells spiked in the blood remains less than 40%, which might not be enough for clinical application.…”

“…In fact, our previous experimental studies showed that MPM tumor cells were captured with the CTC-chip coated with an Ab against podoplanin that was abundantly expressed on mesothelial cells. 13,14 However, the capture efficacy of tumor cells spiked in the blood remains less than 40%, 13 which might not be enough for clinical application.…”

Using the polymeric circulating tumor cell chip to capture circulating tumor cells in blood samples of patients with colorectal cancer

“…The 'CTC-chip' facilitates efficient and selective separation of CTCs from whole blood samples, mediated by the interaction of target CTCs with antibody-coated microposts under precisely controlled laminar flow conditions (15,31). Subsequently, a novel 'polymeric CTC-chip' was developed to isolate CTCs, with lower cost, high transparency that facilitates observation through the chip, and convertibility of antibodies to coat the surface to arrest cancer cells than that of the existing CTC-chips (32)(33)(34)(35)(36).…”