"Considering the urgent need for early diagnosis of metastatic breast cancer and recent advances in functional nucleic acid-mediated bioassays from our group, we designed the platform and demonstrated its feasibility for CTC detection," Dr. Zai-Sheng Wu of Fuzhou University in China told Reuters Health by email.
As reported in ACS Sensors, the team used a breast cancer cell line, BT474, which produces large amounts of ErbB-2 and EpCAM. They isolated the cells from a buffer solution using magnetic beads attached to antibodies against ErbB-2.
Next, they added an aptamer - a single-stranded DNA molecule - that selectively targets EpCAM. The strand also carries short DNA sequences capable of generating an enzymatic amplification reaction, thereby creating additional copies that can bind to fluorescent probes. Using fluorescence spectrometry, the team could detect as few as nine breast cancer cells in 200 microliters of buffer solution.
When they spiked breast cancer cells into whole blood, they observed a similar fluorescent signal as in the buffer, suggesting, they say, "that the newly developed...assay system is suitable for screening CTCs in complex environments and is expected to be a promising tool for estimating distant metastasis and predicting the recurrence of tumors."
Dr. Wu said, "The detection of CTCs from patients with breast cancer remains technically challenging because of their heterogeneity. Nevertheless, our group is already collaborating with scientists in Fujian Cancer Hospital to promote the transition from the laboratory to clinic trials."
Dr. Annette Lee, Associate Professor, Institute of Molecular Medicine at the Feinstein Institutes for Medical Research in Manhasset, New York, commented in an email to Reuters Health, "The new platform ...is a unique approach to quantifying CTCs."
The data are based on a breast cancer cell line that highly expresses HER-1 and EpCAM2, she noted. "Although the authors show these cells can be detected with this assay when added to whole blood, the paper would have been significantly stronger with results from blood samples from women with breast cancer," she said. "HER-2 is not highly expressed in all breast cancer cells - e.g., triple negative breast cancer - and it would be important to know the minimal level of receptor expression needed for detection."
The next steps, in Dr. Lee's view, "would be to assay blood samples from women with breast cancer, and possibly test other breast cancer cell receptors (ER and PR) alone and in combination, to determine the limits of detection and whether combinations of multiple receptor antibodies can be used to detect breast cancer cells with variable levels of receptor expression."
"This assay is not ready for prime time," she added. "However, it does have the potential to significantly increase the specificity and sensitivity of liquid biopsy samples to monitor disease states in breast cancer and possibly other cancers in the future."
Dr. Sandip Patel, Co-Leader, Experimental Therapeutics at the University of San Diego and Deputy Director, San Diego Center for Precision Immunotherapy, also commented by email. "The ability to detect rarer CTC populations would be helpful for risk stratification after surgery and to facilitate diagnosis or biomarker testing when there is limited tissue."
"Comparison of this technique using human blood samples from the clinic and CTC detection with this platform versus existing platforms would be a key step," he said, "then focusing on the clinical impact of more sensitive CTC detection, perhaps to determine need for adjuvant chemotherapy in certain post-operative settings."
SOURCE: https://bit.ly/2KHzWe7 ACS Sensors, online November 18, 2020.
By Marilynn Larkin
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