Scientists at St. Jude Children's Research Hospital have answered a central question in cancer biology: whether normal stem cells can give rise to tumors. Stem cells are immature cells that can renew themselves and give rise to mature differentiated cells that compose the range of body tissues. In recent years, researchers have developed evidence that cancers may arise from mutant forms of stem cells.
Like a brand-name product instantly identifiable by its trademarked logo, normal and cancerous stem cells display on their surface characteristic proteins, including Prominin1 or CD133. A key question in cancer biology has been whether these so-called cancer stem cells arise from normal stem cells or more mature cancer cells that somehow reacquire the characteristics of stem cells.
In the advanced, online issue of the journal Nature, St. Jude investigators show that Prominin1 marks normal intestinal stem cells and that these cells, when mutated, give rise to intestinal tumors. The finding could also aid in identifying the source of cancer stem cells in the lung, kidney, brain, pancreas and other tissues.
"The idea that cancers might arise from mutant stem cells is an attractive one; but until now the link between normal and cancer stem cells in solid tissues like the intestine was not known," said Richard Gilbertson, M.D., Ph.D., associate member of the St. Jude Developmental Neurobiology and Oncology departments and the paper's senior author. "Our work provides the first direct link between normal solid tissue stem cells and cancer. The fact that this occurs in the intestine is particularly interesting since human intestinal tumors contain Prominin1-expressing cancer stem cells."
In addition to providing insights into the origins of cancer, the work might help scientists identify more effective treatments. "Normal stem cells are designed to withstand environmental insults," Gilbertson said. "Thus cancer stem cells might use these same mechanisms to resist chemotherapy and radiotherapy. Remnant cancer stem cells might therefore cause tumors to relapse and re-grow following treatment. If we could kill these cancer stem cells, we might be able to prevent relapse. Understanding the link between normal and cancerous stem cells should help us target the latter while preserving the former."
Working with mice, the researchers inserted a genetic switch that enabled them to selectively turn on a colored tracer molecule only in cells that were expressing, or had expressed, Prominin1. These tracer experiments revealed that Prominin1 cells generate the covering of the entire small intestine and are therefore the stem cell of this tissue.
Next, the researchers switched on cancer-producing machinery in the Prominin1 intestinal stem cells and used a fluorescent tracer to follow the offspring of these cells. Those studies revealed that the stem cells stopped making normal intestine and made tumors instead. "We saw a dramatic change in these laboratory models," Gilbertson said. "The tumorous tissue ultimately replaced the entire normal intestine. In terms of clinical importance, now that we have isolated both the normal, parental stem cells and the cancer stem cells, we can begin screening compounds that will affect the malignant stem cell but not the normal stem cell."
More broadly, Prominin1 might prove to be a useful marker to trace cancer stem cells in the kidney, brain, pancreas and other tissues. The researchers are also exploring the use of stem cell markers in diseases other than cancer. "As we develop these kinds of characteristic markers for stem cells, we might be able to use them to isolate stem cells capable of regenerating healthy tissue in patients who suffer diabetes or other diseases due to organ failure," Gilbertson said.
Carrie Strehlau | EurekAlert!
Complementing conventional antibiotics
24.05.2018 | Goethe-Universität Frankfurt am Main
Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
24.05.2018 | Ecology, The Environment and Conservation
24.05.2018 | Medical Engineering
24.05.2018 | Physics and Astronomy