CTCs in a Spin
A microfluidic device isolates circulating tumor cells from the blood with micro-whirlpools in 15 minutes, facilitating further research into the link between CTC protease expression and metastasis
Luke Turner | | Longer Read
At a Glance
- Liquid biopsies currently focus on the number of circulating tumor cells (CTCs) in the blood to detect the spread of a tumor
- Cancer cells secrete proteases that are linked with metastasis; however, the success of protease inhibitors has been inconsistent because of tumor cell heterogeneity
- A new microfluidics device that isolates CTCs can analyze the proteases they secrete to gain insight into their function and heterogeneity
- Using the technology, researchers found that matrix metalloproteases secreted by CTCs indicate active malignant processes
Australian pathologist Thomas Ashworth first described “cells identical with those of the cancer itself” in the blood in 1869 (1). Today, the presence of such circulating tumor cells (CTCs) is associated with the aggressive spread of a tumor, which is thought to occur when CTCs secrete proteolytic enzymes that facilitate invasion. These matrix metalloproteases (MMPs) are synthesized as inactive preproenzymes, but become activated by pro-matrixins once secreted and then degrade extracellular matrix barriers.
Previous efforts to quantify the number of CTCs in patients, with the goal of predicting treatment effectiveness, have yielded mixed results. This is partly because of CTC phenotype heterogeneity; not all cells have a phenotype optimized for extravasation. Similarly, clinical trials of MMP inhibitors have not been overwhelmingly successful thus far, because CTCs vary in their secretion of MMPs. What if we could establish the level of MMP secretion by patients’ CTCs – rather than simply measuring the number of CTCs? And would such a tool allow us to identify patients who would benefit from MMP inhibitors?
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