Capture of mesothelioma cells with 'universal' CTC-chip

Our plain-English summary of Capture of mesothelioma cells with 'universal' CTC-chip, by K. Yoneda, Y. Chikaishi, T. Kuwata, et al (Oncology Letters, 2018).

The study

• Authors: K. Yoneda, Y. Chikaishi, T. Kuwata, T. Ohnaga, F. Tanaka
• Journal: Oncology Letters
• Published: 2018;15(2):2635-2640
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a laboratory study of cultured cancer cells, not of patients or of asbestos exposure. The authors tested their 'CTC-chip', meant to catch tumor cells circulating in blood. The chip can be coated with different antibodies that grab markers on cells. About 500 labeled cells in buffer solution (not blood) were run through chips coated with antibodies against EpCAM, podoplanin or mesothelin, in triplicate. The mesothelioma cell line ACC-MESO-1 lacked EpCAM and modestly expressed podoplanin. The podoplanin-coated chip caught an average of 52.7% of these cells, versus 3.5% for the EpCAM-coated chip (P=0.005). That was lower than the 78.3% the authors' earlier study reported for another mesothelioma line, ACC-MESO-4. The mesothelin-coated chip caught 2.9% to 5.4% of cells from one lung cancer line and two mesothelioma lines, which the authors attributed mainly to low mesothelin on the cells. The authors concluded the chip might be a useful less-invasive blood-based tool for diagnosing mesothelioma. They stated that methods for patient samples were still under consideration.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory experiment on cultured human cell lines, with capture tests repeated in triplicate
• Who was studied: Two human mesothelioma cell lines (ACC-MESO-1 and ACC-MESO-4) and one human lung adenocarcinoma cell line (PC-9); no human subjects. Some additional tests (data not shown) used a further mesothelioma line, MSTO-211H.
• Exposure: No asbestos exposure was studied. The test condition was a microfluidic CTC-chip coated with an anti-EpCAM, anti-podoplanin or anti-mesothelin antibody. About 500 labeled tumor cells suspended in 1 ml of phosphate-buffered saline (not blood) were run through each chip.
• Main results:
  • On flow cytometry, the mesothelioma cell line ACC-MESO-1 did not express EpCAM and modestly expressed podoplanin.
  • PC-9 lung adenocarcinoma cells did not express mesothelin; the mesothelioma lines ACC-MESO-1 and ACC-MESO-4 weakly expressed mesothelin.
  • For ACC-MESO-1 cells in buffer, the podoplanin-chip had an average capture efficiency of 52.7%. This was significantly higher than the EpCAM-chip's 3.5% (P=0.005, Mann-Whitney U-test).
  • The authors described the 52.7% podoplanin-chip capture of ACC-MESO-1 as only modest. They compared it with 78.3% for ACC-MESO-4 cells, a figure taken from their previous study.
  • The mesothelin-chip captured an average of 2.9% of PC-9 cells, 4.3% of ACC-MESO-1 cells and 5.4% of ACC-MESO-4 cells (P=0.329, Kruskal-Wallis H-test). The authors judged that it failed to provide effective capture.
  • In additional tests whose data were not shown, the podoplanin-coated chip captured 8.3% (51 of 611) of MSTO-211H mesothelioma cells. The authors reported that these cells did not express podoplanin.
  • Also with data not shown, the mesothelin-chip (clone K1) captured 6.2% (28 of 453) of MSTO-211H cells.
  • With a second anti-mesothelin antibody (clone 5B2), capture efficiency was 14.3% (12 of 84) for ACC-MESO-1 cells and 7.3% (6 of 82) for ACC-MESO-4 cells (data not shown).
• The authors' conclusion: The authors concluded that the 'universal' CTC-chip might be a useful less-invasive, blood-based method in the diagnosis of malignant mesothelioma.
• Limitations the authors state:
  • The authors stated that optimal detection methods for clinical (patient) samples were still under consideration. Only cultured cells in buffer were tested here.
  • The authors stated that other mesothelioma cell lines still need to be tried.
  • The authors attributed the mesothelin-chip's failure mainly to low mesothelin expression on the mesothelioma cells tested. They said other cell lines with more mesothelin, or other mesothelin antibodies, need to be examined.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Podoplanin (D2-40), Mesothelin.

Related studies

• EpCAM-independent capture of circulating tumor cells with a 'universal CTC-chip' — Y. Chikaishi, K. Yoneda, et al. (2017)
• Detection of circulating tumor cells with a novel microfluidic system in malignant pleural mesothelioma — K. Yoneda, T. Kuwata, et al. (2019)
• Analysis of asbestos-induced gene expression changes in bronchiolar epithelial cells using laser capture microdissection and quantitative reverse transcriptase-polymerase chain reaction — C.B. Manning, B.T. Mossman, et al. (2006)
• Porous Zero-Mode Waveguides for Picogram-Level DNA Capture — V. Jadhav, D.P. Hoogerheide, et al. (2019)
• Laser capture microdissection reveals dose-response of gene expression in situ consequent to asbestos exposure — Q. Yin, A.R. Brody, et al. (2007)
• Capture efficiency of portable high-efficiency air filtration devices used during building construction activities — D.A. Newcomer, P. LaPuma, et al. (2018)

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