Circulating tumor cells: researchers develop mechanism for characterizing function

A team of researchers from the University of California (CA, USA) have created a method of measuring how circulating tumor cells (CTCs) perform functions that drive cancer, such as producing matrix metalloproteases (MMPs). The findings were published in the Proceedings of the National Academy of Sciences. 

CTCs have the potential to provide vital information about an individual’s specific cancer. However, up until now researchers have been unable to reliably access information on how these cells behave, in part because of a single CTC produces only a small number of molecules. Traditional tests to measure the molecules’ activity when cells are in a large pool of fluid don’t work because the molecules are diluted to small concentrations.

“Liquid biopsies aren’t new, but what’s new here is that we’re getting insight into the function of the circulating tumor cell,” explained one of the paper’s authors, Matthew Rettig UCLA Jonsson Comprehensive Cancer Center (CA, USA). “If we can describe the motion and activity of a patient’s tumor, we can get a handle on how aggressive it is, how it may evolve and metastasize, and ultimately, what kind of therapeutic interventions could be appropriate to treat the disease.”

In this study, the researchers used a device that creates micro-whirlpools to isolate the circulating tumor cells from the blood. The team then was able to measure the small number of molecules by putting each cell in an individual drop of fluid thousands of times smaller than traditional laboratory tubes, allowing the molecules to stay in a highly concentrated state, rather than getting diluted, when the cell secretes.

“We’re looking at individual cells and then looking at small numbers of molecules that each individual cell is producing and secreting, and that gives us very precise information,” explained study lead Dino Di Carlo (UCLA Jonsson Comprehensive Cancer Center).

The team then investigated whether their new approach could detect the activity of MMPs in advanced prostate cancer patients. The study cohort involved seven individuals with late-stage prostate cancer and four who were healthy.

The new technique revealed that MMPs were produced at higher levels in those with advanced disease. This also indicated a correlation between high MMP activity in circulating tumor cells and poor prognosis.

Although it was a small study, the researchers state that the results prove that the technique merits further testing.

“With this type of measurement tool, you could potentially figure out which drugs would work best for each person before even starting treatment,” DiCarlo added. “Cancer isn’t a one-size-fits all disease. This tool can really help us customize treatments and only use drugs targeting proteases on the patients who would actually benefit from it.”

This study is among the first to characterize and quantify activity of enzymes produced by circulating tumor cells, an important step toward clarifying the biology of how cancer spreads.

“Being able to understand the biology of metastasis will allow us to intervene better and continue to make better diagnostic tools to help patients,” Di Carlo concluded.