Detection of Circulating Tumor Cells (CTCs) in Malignant Pleural Mesothelioma (MPM) with the "Universal" CTC-Chip and An Anti-Podoplanin Antibody NZ-1.2

Our plain-English summary of Detection of Circulating Tumor Cells (CTCs) in Malignant Pleural Mesothelioma (MPM) with the "Universal" CTC-Chip and An Anti-Podoplanin Antibody NZ-1.2, by T. Kuwata, K. Yoneda, M. Mori, et al (Cells, 2020).

The study

• Authors: T. Kuwata, K. Yoneda, M. Mori, M. Kanayama, K. Kuroda, M.K. Kaneko, Y. Kato, F. Tanaka
• Journal: Cells
• Published: 2020;9(4)
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Circulating tumor cell (CTC) is a potentially useful surrogate of micro-metastasis, but detection of rare tumor cells contaminated in a vast majority of normal hematologic cells remains technical challenges. To achieve effective detection of a variety of CTCs, we have developed a novel microfluidic system (CTC-chip) in which any antibody to capture CTCs is easily conjugated. In previous studies, we employed an antibody (clone E-1) against podoplanin that was strongly expressed on mesothelioma cells. The CTC-chip coated by the E-1 antibody (E1-chip) provided a modest sensitivity in detection of CTCs in malignant pleural mesothelioma (MPM). Here, to achieve a higher sensitivity, we employed a novel anti-podoplanin antibody (clone NZ-1.2). In an experimental model, MPM cells with high podoplanin expression were effectively captured with the CTC-chip coated by the NZ-1.2 antibody (NZ1.2-chip). Next, we evaluated CTCs in the peripheral blood sampled from 22 MPM patients using the NZ1.2-chip and the E1-chip. One or more CTCs were detected in 15 patients (68.2%) with the NZ1.2-chip, whereas only in 10 patients (45.5%) with the E1-chip. Of noted, in most (92.3%, 12/13) patients with epithelioid MPM subtype, CTCs were positive with the NZ1.2-chip. The CTC-count detected with the NZ1.2-chip was significantly higher than that with the E1-chip (p = 0.034). The clinical implications of CTCs detected with the NZ1.2-chip will be examined in a future study.

In plain English

This laboratory and patient study from Japan tested a blood test for finding circulating tumor cells (tumor cells shed into the bloodstream) in malignant pleural mesothelioma. It did not examine asbestos exposure. The test uses a microfluidic 'CTC-chip' coated with an antibody against podoplanin, a protein found on mesothelioma cells. The authors compared a newer antibody (NZ-1.2) with one from their earlier work (E-1). In laboratory tests, epithelioid mesothelioma cell lines were captured efficiently (62.8% to 97.9%), while non-epithelioid lines were captured poorly. In blood from 22 patients, tumor cells were found in 15 (68.2%) with the NZ-1.2 chip and 10 (45.5%) with the E-1 chip, including 12 of 13 patients with the epithelioid subtype. Median counts were 2 and 0 cells per 1 mL of blood (p = 0.034). The authors concluded that the NZ-1.2 chip performed better. They called their results preliminary because the group was small, each sample was tested only once, the chip detected few cells in non-epithelioid disease, and they did not confirm that the captured cells were truly mesothelioma cells.

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 experiments on mesothelioma cell lines plus a retrospective evaluation of blood samples from patients, comparing two antibody-coated CTC-chips on the same blood sample
• Who was studied: 22 patients with malignant pleural mesothelioma (MPM), treated between November 2016 and September 2018; 21 men and 1 woman, median age 68.5 years (54 to 79); 13 epithelioid, 4 biphasic, 5 sarcomatoid. The study was approved by the Ethics Committee of the University of Occupational and Environmental Health, Japan. Five MPM cell lines were also tested.
• Exposure: Not reported. The article does not assess asbestos or any other exposure. It evaluates a blood test, not a cause of disease.
• Main results:
  • With the NZ-1.2 chip, epithelioid cell lines were captured with efficiencies of 62.8% (ACC-MESO-1), 97.9% (ACC-MESO-4) and 97.6% (NCI-H226). Capture of non-epithelioid cell lines, which showed no significant podoplanin, was low.
  • Non-epithelioid cell lines (NCI-H28 and MSTO-211H) had low capture efficiency on the NZ-1.2 chip.
  • Among the 22 patients, CTCs were detected in 10 (45.5%) with the E1-chip and in 15 (68.2%) with the NZ1.2-chip.
  • CTCs were detected with either chip in 19 of 22 patients (86.4%).
  • With the NZ1.2-chip, CTCs were detected in 12 of 13 epithelioid MPM patients (92.3%).
  • Across all 22 patients, the median CTC-count was 0 (range 0 to 7) with the E1-chip and 2 (range 0 to 11) with the NZ1.2-chip, reported as significantly higher with the NZ1.2-chip (p = 0.034).
  • In the 13 epithelioid patients, the median CTC-count was 0 with the E1-chip and 3 with the NZ1.2-chip (p = 0.013).
  • With the NZ1.2-chip, the median CTC-count was 3 for epithelioid and 0 for biphasic or sarcomatoid patients; the count was significantly higher in epithelioid patients.
  • The CTC-count did not differ significantly by clinical stage. Among epithelioid patients it trended higher in stage III and IV, but this was not statistically significant (p = 0.051).
• The authors' conclusion: The authors concluded that the NZ1.2-chip achieved higher performance in capturing CTCs in MPM, and that future studies may reveal the clinical relevance of these cells.
• Limitations the authors state:
  • Only 22 patients, too few for any definitive conclusion; the authors call the results preliminary.
  • The test was done only once on a single blood sample per patient, so reproducibility was not assessed.
  • The clinical impact of the test needs longer follow-up.
  • The chip may not detect CTCs sensitively in non-epithelioid MPM (sensitivity 33.3%).
  • The authors did not confirm that captured cells were true MPM cells rather than non-malignant cells, such as reactive mesothelial cells, that can also express podoplanin.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Podoplanin (D2-40), Metastasis, Mesothelioma, Epithelioid.

Related studies

• EpCAM-independent capture of circulating tumor cells with a 'universal CTC-chip' — Y. Chikaishi, K. Yoneda, et al. (2017)
• Novel circulating tumor cell-detection chip combining conventional podoplanin and EGFR antibodies for all histological malignant pleural mesothelioma — M. Kanayama, R. Oyama, et al. (2021)
• Detection of circulating tumor cells with a novel microfluidic system in malignant pleural mesothelioma — K. Yoneda, T. Kuwata, et al. (2019)
• Circulating tumor cells (CTCs) in malignant pleural mesothelioma (MPM) — K. Yoneda, F. Tanaka, et al. (2014)
• Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model — S. Abe, M.K. Kaneko, et al. (2016)
• Therapeutic efficacy evaluation of radioimmunotherapy with 90 Y-labeled anti-podoplanin antibody NZ-12 for mesothelioma — H. Sudo, A.B. Tsuji, et al. (2019)

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