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A fluorescent probe, called AlDeSense, has demonstrated the ability to find and track cancer stem cells (CSCs) in cultures of multiple human cancer cell lines as well as in live mice. The new probe is a small molecule that binds to an enzyme (ALDH1A1) that is related to the property of stemness in cancer cells. The probe becomes activated and emits a fluorescent signal only when it reacts with the target enzyme, which CSCs produce in high concentrations.
Researchers at the University of Illinois at Urbana-Champaign, who developed the probe, targeted an enzyme that was experimentally shown to be a probable marker for stemness across many forms of cancer. AlDeSense will selectively turn on in CSCs when upregulated ALDH1A1 activity occurs.
Cancer stem cells can be difficult to distinguish from standard tumor cells with conventional imaging (left), but the AlDeSense marker makes the cancer stem cells light up with fluorescence (right). Courtesy of Chelsea Anorma, University of Illinois.
Using the probe in tandem with flow cytometry and confocal imaging, the team identified CSCs at the cellular level and monitored the states of the CSCs in animal models.
The team found and tracked CSCs in tissue removed from mice for biopsy and in live mice with metastatic tumors. Researchers were able to follow CSCs from injection to tumor, as they spread through the bodies of the mice, to obtain new information about CSC behavior.
“Through this study, we can see that the stemness properties are maintained in the population, even after they metastasize. There’s something about the environment in the body that supports stem cell characteristics. With AIDeSense, now we can profile that environment,” said professor Jefferson Chan.
AlDeSense exhibits a 20-fold fluorescent enhancement when treated with the target enzyme ALDH1A1. Researchers further established that AlDeSense is selective against a panel of common ALDH isoforms.
University of Illinois researchers developed a molecular probe that can tag and track elusive cancer stem cells in both cell cultures and live organisms. From left: Chemistry professor Jefferson Chan, graduate students Chelsea Anorma and Thomas Bearrood, and postdoctoral researcher Jamila Hedhli. Courtesy of L. Brian Stauffer.
The team is evaluating whether the use of AlDeSense to track CSC populations in tumors can predict prognosis in dogs with lymphoma. It is also working to enable the probe for other functions, such as the capability to selectively kill cancer stem cells.
“Another thing we’re pursuing is screening for inhibitors or drugs that can kill cancer stem cells by targeting this enzyme. Since we know that our probe only interacts with that one target, we can use the probe to look for a drug that can inhibit this enzyme and verify it in cells and in live animals. The multiscale utility of the molecule makes it unique,” said Chan.
The research was published in ACS Central Science (doi: 10.1021/acscentsci.8b00313).READ MORE