Yoneda Kazue, Chikaishi Yasuhiro, Kuwata Taiji, Ohnaga Takashi, Tanaka Fumihiro
Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan.
Central Research Institute, Toyama Industrial Technology Center, Takaoka, Toyama 933-0981, Japan.
Oncol Lett. 2018 Feb;15(2):2635-2640. doi: 10.3892/ol.2017.7619. Epub 2017 Dec 14.
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.
恶性间皮瘤（MM）是一种侵袭性很强的恶性肿瘤，主要与职业性接触石棉有关。开发有效且非侵入性的诊断方法是职业医学中的一个重要问题。循环肿瘤细胞（CTC）是从原发性肿瘤脱落并在外周血中循环的肿瘤细胞，其检测可能比恶性肿瘤更早，并且CTC的检测可能为MM的诊断提供新的见解。在先前一项评估使用广泛的“CellSearch”系统检测CTC的临床效用的研究中，作者指出其在MM诊断方面有显著但不足的能力，表明需要更灵敏的系统。因此，作者开发了一种新型微流控系统来捕获CTC（CTC芯片），并证明该CTC芯片通过结合抗足板蛋白抗体有效地捕获了血液中加入的MM细胞（ACC-MESO-4）。本研究结果表明，涂有抗足板蛋白抗体的CTC芯片捕获了另一种MM细胞（ACC-MESO-1）。然而，捕获效率低于ACC-MESO-4。此外，使用抗间皮素抗体来捕获CTC，但涂有抗间皮素抗体的CTC芯片未能有效捕获MM细胞，可能是由于间皮素表达较低。总体而言，CTC芯片可通过结合任何针对CTC上表达的抗原的抗体来捕获特定类型的CTC，并且可能是用于诊断包括MM在内的恶性肿瘤的有用系统。
