Nav: Home

New technique visually depicts how cancer cells grow and spread in colon tissue

December 02, 2019

DURHAM, N.C. - Duke Cancer Institute researchers have observed how stem cell mutations quietly arise and spread throughout a widening field of the colon until they eventually predominate and become a malignancy.

Using an innovative modeling system in mice, the researchers visually tagged colon cancer mutations by causing stem cells to glow. Mutations found in colon cancer were then visualized in the animals, illuminating a sort of tournament-to-the-death underway in the intestine in which one or another mutation prevailed over the others to become the driving force of a malignancy.

"This study provides new insight into the previously invisible process in which mutant precancerous stem cells spread throughout the colon and seed cancer," said Joshua Snyder, Ph.D., assistant professor in the departments of Surgery and Cell Biology at Duke and corresponding and co-senior author of a study publishing online Dec. 2 in the journal Nature Communications.

"Our technique sets a firm foundation for testing new therapies that interrupt this early, pre-malignant process. We hope to one day target and eliminate these stealth precancerous cells to prevent cancer," Snyder said.

Snyder and colleagues -- including co-senior author H. Kim Lyerly, M.D., George Barth Geller Professor at Duke ¬-- applied the molecular dyeing technique in a new way, tagging several common colon cancer mutations in the stem cells of a single tumor to create a fluorescent barcode.

When transferred to a mouse, the rainbow of fluorescent stem cells could be visually tracked, revealing the cellular and molecular dynamics of pre-cancerous events.

In this way, the researchers found key differences in how the intestinal habitats common to babies and adults grow pre-cancerous fields of mutant cells. At a critical period, newborns are sensitive to the effects of mutations within intestinal stem cells. This insidiously seeds large fields of premalignant mutated cells throughout the intestine -- a process called field cancerization -- that dramatically increases cancer risk. These fields of mutated cells can grow and spread for years without being detected by current screening technologies; often, they remain harmless, but under proper conditions, can rapidly become cancerous later in adults.

The researchers also observed that some colon cancer mutations found in patients can lead to a striking increase in the fertility of the environment surrounding precancerous fields. Ultimately, this leads to the rapid spread of fields throughout the intestine, with lethal consequences.

Certain common mutations that arise from external sources, such as an injury or an environmental exposure, could also disrupt the environment surrounding the stem cell and lead to the rapid growth and spread of precancerous fields. These occurrences can be especially lethal in adults and occur much more rapidly than previously expected - as if dropping a match on a drought-stricken forest.

"Field cancerization has been suggested to be the defining event that initiates the process of cancer growth, including cancers of the breast, skin and lung," Snyder said. "Our technique allows us to model how premalignant cells compete and expand within a field by simple fluorescent imaging, potentially leading to earlier diagnosis and treatment."

Snyder said additional studies are underway using the fluorescent barcoding to view the cancer fields in breast cancer, aiming to learn more about when a pre-cancerous condition known as ductal carcinoma in situ is driven by malignant vs. benign mutations.

In addition to Snyder and Lyerly, study authors include Peter G. Boone, Lauren K. Rochelle, Veronica Lubkov, Wendy L. Roberts, P.J. Nicholls, Cheryl Bock, Mei Lang Flowers, Richard J. von Furstenberg, Joshua D. Ginzel, Barry R. Stripp, Pankaj Agarwal, Alexander D. Borowsky, Robert D. Cardiff, Larry S. Barak and Marc G. Caron.
-end-
The work was supported by the National Cancer Institute (512-CA100639-10, 1K22CA212058, R21CA173245, 1R33CA191198, NICHD 5T32HD040372), Sage Biosciences (3U24CA209923-01S1), the Department of Defense (W81XWH-12-1-0447) and Duke Surgery.

Duke University Medical Center

Related Stem Cells Articles:

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.
First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.
Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.
New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.
NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
In mice, stem cells seem to work in fighting obesity! What about stem cells in humans?
This release aims to summarize the available literature in regard to the effect of Mesenchymal Stem Cells transplantation on obesity and related comorbidities from the animal model.
TSRI researchers identify gene responsible for mesenchymal stem cells' stem-ness'
Researchers at The Scripps Research Institute recently published a study in the journal Cell Death and Differentiation identifying factors crucial to mesenchymal stem cell differentiation, providing insight into how these cells should be studied for clinical purposes.
More Stem Cells News and Stem Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.