Cancer stem cells (CSCs) that remain undetected after treatment leads to a resurgence of more aggressive and resistant tumors. Moreover, CSCs can be difficult to distinguish from standard tumor cells using conventional imaging. In new findings published in ACS Central Science, a University of Illinois-led team of researchers have developed a molecular probe that can light up CSCs in vivo, allowing them to be identified and tracked.
"It's really the first time to be able to look at cancer stem cells in the complicated environment where they live—not only in cell cultures or artificial tumor environments," said study senior co-author Jefferson Chan. "Seeing them is the first step toward understanding them. Now we can see where they're hiding out, how they change as the disease is progressing or how they respond when you apply treatment."
The novel probe, called AlDeSense, is a fluorescent probe that responds to the activity of the enzyme aldehyde dehydrogenase 1A1 (ALDH1A1). AlDeSense exhibits a 20-fold fluorescent enhancement when treated with ALDH1A1, whose expression is greatly elevated in CSCs.
Experiments further demonstrate that ALDH1A1 appears to be a marker of stemness across many types of cancer cells, a feat that may allow AlDeSense to be used broadly for clinical imaging. Flow cytometry and confocal imaging work using AlDeSense have successfully tracked CSCs in mouse biopsies and in live mice.
"Prior to this study, nobody knew what happens between injection of cancer stem cells and removal of a tumor. There are a lot of models that hypothesize about how cancer stem cells differentiate and grow, but limited experimental data," said Chan. "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 AlDeSense, now we can profile that environment."
The team now tests the application of AlDeSense in tracking CSC populations in tumors to predict prognosis in dogs with lymphoma.
Image: The AlDeSense marker makes the cancer stem cells light up with fluorescence. Image courtesy of Chelsea Anorma, University of Illinois.