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Researchers Use 'NanoVelcro' Chip to Capture Prostate Cancer CTCs for Single-Cell Sequencing


A team led by investigators at Cedars-Sinai Medical Center and the University of California, Los Angeles has developed a new approach for analyzing circulating tumor cells obtained from prostate cancer patients using chip- and sequencing-based applications.

The team described how it combined its internally developed "NanoVelcro" chip, laser capture microdissection, and next-generation sequencing to obtain and study CTCs in a recent paper in the journal Advanced Materials.

Edwin Posadas, medical director of the urology cancer program at Cedars-Sinai, said that the team developed the approach to overcome limitations with current methods to capture and analyze CTCs.

"The issue is that the field is rather old," Posadas told BioArray News this week. "The CTC field has been around since the 1970s, but the cells that are obtained using current methods are low in in number, and because they are treated chemically, they are not suitable for future study," he said. "These limitations pushed our groups to develop this new technology."

Posadas noted that the main approach used for capturing CTCs is Johnson & Johnson's CellSearch assay, which relies on an immunomagnetic agent to capture the cells followed by multiplexed immunocytochemistry studies to characterize them.

At the same time, Posadas said that prostate cancer researchers require access to prostate cancer CTCs in order to gauge the impact of therapy on tumors that are difficult to biopsy as they have, in some cases, spread to the bone, where there is limited tissue available.

"Prostate cancer is the most common cancer in American men, and yet we are stuck in the 1950s in terms of how we classify the disease," said Posadas. "This technology, which allows us to do this, is a significant advancement for prostate cancer as a field."

To capture the CTCs, the research team relied on the NanoVelcro chip, a nanotechnology tool developed at UCLA that is being commercialized by spinout Cytolumina Technologies. Patients' blood was pumped through the chip, and the microvilli protruding from the CTCs was captured by the nanofiber structures on the device's surface. Laser capture dissection was the used to remove CTCs for isolation, purification, and subsequent single-cell sequencing.

Hsian-Rong Tseng, an associate professor of medical pharmacology at UCLA and founder of Cytolumina, in a statement called the team's work a "scientific breakthrough" as it demonstrated the "ability to isolate pure CTCs and maintain their integrity for sophisticated genomic and behavioral analyses."

Posadas said that the team would like to use the approach to help guide treatment for prostate cancer patients in the future.

"If you are able to take a small cell and obtain genomic information from the tumor, you may be able to make some powerful molecular characterizations," he said.

Currently, the team is involved in two follow-on projects to the initial study, Posadas said. One is an effort with partners at BGI to describe prostate cancer CTCs and their response to different therapies over time.

The other is a collaboration with Exelixis, a Bay Area biopharmaceutical firm that has developed a compound for treating prostate, thyroid, and kidney cancer. The research team will recruit 40 patients in the next two years to study the impact of the compound on prostate cancer bone metastases, Posadas said.