EpCAM-independent capture of circulating tumor cells with a 'universal CTC-chip'

Our plain-English summary of EpCAM-independent capture of circulating tumor cells with a 'universal CTC-chip', by Y. Chikaishi, K. Yoneda, T. Ohnaga, et al (Oncology Reports, 2017).

The study

• Authors: Y. Chikaishi, K. Yoneda, T. Ohnaga, F. Tanaka
• Journal: Oncology Reports
• Published: 2017;37(1):77-82
• Cited by: 41 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Capture of circulating tumor cells (CTCs), which are shed from the primary tumor site and circulate in the blood, remains a technical challenge. CellSearch® is the only clinically approved CTC detection system, but has provided only modest sensitivity in detecting CTCs mainly because epithelial cell adhesion molecule (EpCAM)-negative tumor cells may not be captured. To achieve more sensitive CTC‑capture, we have developed a novel microfluidic platform, a 'CTC-chip' comprised of light-curable resins that has a unique advantage in that any capture antibody is easily conjugated. In the present study, we showed that EpCAM-negative tumor cells as well as EpCAM-positive cells were captured with the novel 'universal CTC-chip' as follows: i) human lung cancer cells (PC-9), with strong EpCAM expression, were efficiently captured with the CTC-chip coated with an anti-EpCAM antibody (with an average capture efficiency of 101% when tumor cells were spiked in phosphate‑buffered saline (PBS) and 88% when spiked in blood); ii) human mesothelioma cells (ACC-MESO-4), with no EpCAM expression but with podoplanin expression, were captured with the CTC-chip coated with an anti-podoplanin antibody (average capture efficiency of 78% when tumor cells were spiked in PBS and 38% when spiked in blood), whereas ACC-MESO-4 cells were not captured with the CTC-chip coated with the anti-EpCAM antibody. These results indicate that the novel 'CTC-chip' can be useful in sensitive EpCAM-independent detection of CTCs, which may provide new insights into personalized medicine.

In plain English

This was a laboratory study of a microfluidic device, the 'CTC-chip', designed to capture tumor cells circulating in the blood. The approved CellSearch system relies on a cell marker called EpCAM. This chip can instead be coated with different capture antibodies. The authors tested two human cell lines. PC-9 lung adenocarcinoma cells carried EpCAM. ACC-MESO-4 malignant pleural mesothelioma cells lacked EpCAM but strongly expressed another marker, podoplanin. Cells were added to a salt solution (PBS) or to blood from one healthy volunteer, who was an author. In PBS, the chip coated with anti-EpCAM antibody captured an average of 101.1% of PC-9 cells but only 3.0% of mesothelioma cells. The chip coated with anti-podoplanin antibody captured 78.3% of mesothelioma cells. In blood, the anti-podoplanin chip captured 38.4% of mesothelioma cells, compared with 2.2% for the anti-EpCAM chip, which captured 88.0% of PC-9 cells. No patients and no asbestos exposure were studied. The authors concluded that EpCAM-negative cells could be captured this way. They stated that capture from blood should be improved and that testing in patients' blood is still needed.

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 (in vitro) experiment testing a tumor-cell capture device with cancer cell lines added to fluid or blood
• Who was studied: Two human cell lines: PC-9 (lung adenocarcinoma) and ACC-MESO-4 (malignant pleural mesothelioma). 1,500 cells were suspended in 3 ml of PBS or in 3 ml of blood from one healthy volunteer (an author). Japan.
• Exposure: Not an asbestos exposure study. The study compared two capture antibodies coating the chip: an anti-EpCAM antibody and an anti-podoplanin antibody.
• Main results:
  • PC-9 lung cancer cells strongly expressed EpCAM. ACC-MESO-4 mesothelioma cells did not express EpCAM.
  • ACC-MESO-4 mesothelioma cells strongly expressed podoplanin.
  • In PBS, the chip coated with anti-EpCAM antibody ('EpCAM-chip') captured an average of 101.1% of PC-9 cells.
  • In PBS, the chip coated with anti-EpCAM antibody captured an average of only 3.0% of ACC-MESO-4 mesothelioma cells.
  • In PBS, the chip coated with anti-podoplanin antibody ('podoplanin-chip') captured an average of 78.3% of ACC-MESO-4 mesothelioma cells.
  • In PBS, the chip coated with anti-podoplanin antibody captured an average of only 2.3% of PC-9 cells.
  • In blood, for ACC-MESO-4 mesothelioma cells, the average capture efficiency was 2.2% with the anti-EpCAM antibody chip and 38.4% with the anti-podoplanin antibody chip.
  • In blood, for PC-9 cells, the average capture efficiency was 88.0% with the anti-EpCAM antibody chip and 6.9% with the anti-podoplanin antibody chip.
• The authors' conclusion: The authors concluded that the chip captured EpCAM-positive PC-9 cells when coated with anti-EpCAM antibody, and captured EpCAM-negative ACC-MESO-4 mesothelioma cells when coated with anti-podoplanin antibody.
• Limitations the authors state:
  • Capture efficiency from blood needs to be increased.
  • The chip has not yet been tested on blood from cancer patients.
  • Some mesothelioma cells do not express podoplanin and failed to be captured with an anti-podoplanin antibody.

Topics

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

Related studies

• 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)
• Capture of mesothelioma cells with 'universal' CTC-chip — K. Yoneda, Y. Chikaishi, et al. (2018)
• Circulating endothelial cell (CEC) as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM) — K. Yoneda, F. Tanaka, et al. (2012)
• A liquid biopsy for detecting circulating mesothelial precursor cells: A new biomarker for diagnosis and prognosis in mesothelioma — B.T.V. Duong, L. Wu, et al. (2020)
• Detection of circulating tumour cells in peripheral blood of patients with malignant pleural mesothelioma — J. Raphael, C. Massard, et al. (2015)

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