A protein that stem cells require could be a target in killing breast cancer cellsJune 01, 2017
Cold Spring Harbor, NY - For years, cancer experts have realized that cancerous cells behave in certain ways like stem cells, unspecialized cells that when exposed to certain signals, can "differentiate."
When a stem cell differentiates, it starts down a one-way path that will result in its specialization and eventually its death. For instance, a stem cell in the breast can become a luminal cell, one of the breast's "milk factories." Such cells have a limited life span. Cancer cells resemble stem cells not because they can turn into other cell types, but because in developmental terms, they seem to go in the opposite direction: they begin to run through multiple layers of stop signs and barricades and just keep on multiplying.
Assistant Professor Camila dos Santos of Cold Spring Harbor Laboratory (CSHL) is studying stem cells in the breast for clues about what changes occur when normal breast cells become cancerous. Today, a team led by dos Santos, in collaboration with Professor Gregory Hannon of Cancer Research UK, Cambridge Institute, and Assistant Professor William Pomerantz at the University of Minnesota, identify a protein that they show must be present in order for mammary stem cells to perform their normal functions.
When the researchers genetically removed or chemically inhibited the protein, called BPTF, stem cells could no longer maintain their "renewing" state and began to take on the character of specialized breast cells - and then soon died.
"That was very exciting for us," says dos Santos, "because that's exactly what were want to drive breast cancer cells to do. We want to take away their stem cell-like qualities - especially their ability to multiply indefinitely. We are testing the idea that a drug that inhibits BPTF might have the same effect in cancer cells as in stem cells -it could cause them to differentiate and then die."
When studying how normal cells change into cancer cells, dos Santos and other cancer researchers pay close attention to gene expression. Every cell in the breast, including stem cells, contains the full human genome. One way of thinking about what differentiates a breast cell from a heart cell is that each cell type expresses different subsets of genes.
The same is also true within each organ. In the breast, the ducts designed to carry milk during and after pregnancy are composed of two highly specialized cell types and a niche of stem cells that gives rise to both types. Each of these different cell types expresses different groups of genes at different times over the lifespan of an individual.
The hollow "tube" that forms the milk duct is built from luminal cells; these are surrounded by a thin layer of cells called myoepithelial cells. Receptors on the surface of the myoepithelial cells are designed to interact with a hormone, oxytocin, released during lactation. This interaction causes the myoepithelial cells - on the outer layer of the ductal structure - to contract, squeezing the luminal cells within. Those luminal cells are the breast's milk factories.
BPTF's epigenetic role in exposing and hiding genes
BPTF, identified by Dos Santos and colleagues as essential for mammary stem cell maintenance, is a protein with a very specialized function. It is what biologists call a chromatin remodeling factor. Chromatin is the packaging that enables six linear feet of DNA in each of our cells to be compressed inside the microscopic nucleus.
With so much DNA squished into such a small space, it stands to reason that expressing a gene in the "middle" of the bundle might require loosening the packing material to expose that segment of DNA to the machinery that copies it into an RNA molecule. This copying is the first step in using the gene's "blueprint" to manufacture a needed protein. Chemical modifications to chromatin - and even more specifically, to the histone proteins that provide "spools" around which the DNA is wound - are called epigenetic modifications.
"It has become very clear that the opening up or tightening of chromatin, to expose or hide genes in our chromosomes, plays a role in cancer progression," dos Santos says. "For instance, exposing a gene at a particular moment might help a cancer cell bypass a 'stop sign' in a growth pathway."
The research published today shows that BPTF is part of a regulatory system that opens chromatin and changes gene expression, specifically in mammary stem cells. This opening of the chromatin turns out to be critical in the ability of the stem cell to remain "immortal" - to give rise to daughter stem cells that will also help maintain a tissue such as the breast, and seeding it, at different times of life, with specialized cells. For example, during puberty, when the breast develops, or during pregnancy, when the breast gears up to produce milk.
"We now know that mammary stem cells are highly dependent on BPTF. The next task it to explore if can we use that dependency to target stem cell-like programs in breast cancer cells," dos Santos says.
"BPTF maintains chromatin accessibility and the self-renewal capacity of mammary gland stem cells" appears online June 1, 2017 in Stem Cell Reports. The authors are: Wesley D. Frey Anisha Chaudhry Priscila F. Slepicka, Adam M. Ouellette, Steven E. Kirberger, William C. K. Pomerantz, Gregory J. Hannon and Camila O. dos Santos. The paper can be accessed at: http://www.cell.com/cell-reports/home
About Cold Spring Harbor Laboratory
Founded in 1890, Cold Spring Harbor Laboratory has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,100 people including 600 scientists, students and technicians. The Meetings & Courses Program hosts more than 12,000 scientists from around the world each year on its campuses in Long Island and in Suzhou, China. The Laboratory's education arm also includes an academic publishing house, a graduate school and programs for middle and high school students and teachers. For more information, visit http://www.cshl.edu
Cold Spring Harbor Laboratory
Related Stem Cells Articles:
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St.
In a new Cell Reports paper, a team led by John P.
Related Stem Cells Reading:
Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives
by Neil H Riordan (Author)
Stem cells are the repair cells of your body. When there aren’t enough of them, or they aren’t working properly, chronic diseases can manifest and persist. From industry leaders, sport stars, and Hollywood icons to thousands of everyday, ordinary people, stem cell therapy has helped when standard medicine failed. Many of them had lost hope. These are their stories.
Neil H Riordan, author of MSC: Clinical Evidence Leading Medicine’s Next Frontier, the definitive textbook on clinical stem cell therapy, brings you an easy-to-read book about how and why stem cells work,... View Details
Stem Cells: An Insider's Guide
by Paul Knoepfler (Author)
Stem Cells: An Insider's Guide is an exciting new book that takes readers inside the world of stem cells guided by international stem cell expert, Dr. Paul Knoepfler. Stem cells are catalyzing a revolution in medicine. The book also tackles the exciting and hotly debated area of stem cell treatments that are capturing the public's imagination. In the future they may also transform how we age and reproduce. However, there are serious risks and ethical challenges, too. The author's goal with this insider's guide is to give readers the information needed to distinguish between the... View Details
The Stem Cell Revolution
by Mark Berman MD (Author), Elliot Lander MD (Contributor)
The book describes the journey into the growing arena of clinical stem cell therapy by highlighting not only the road that brought a team of physicians together but also real stories from a number of their patients that were given their health back through the magic of stem cell therapy. Your fat is loaded with stem cells that can be used now to treat and reverse a large number of inflammatory and degenerative conditions. Most people have no idea that these magical cells actually exist right within our bodies. They think that they must wait until Big Pharma or a university PhD manufactures... View Details
Stem Cells For Dummies
by Lawrence S.B. Goldstein (Author), Meg Schneider (Author)
The first authoritative yet accessible guide to this controversial topic
Stem Cell Research For Dummies offers a balanced, plain-English look at this politically charged topic, cutting away the hype and presenting the facts clearly for you, free from debate. It explains what stem cells are and what they do, the legalities of harvesting them and using them in research, the latest research findings from the U.S. and abroad, and the prospects for medical stem cell therapies in the short and long term.Explains the differences between adult stem cells and embryonic/umbilical... View Details
Stem Cells Are Everywhere
by Irv Weissman MD (Author)
An engaging introduction to stem cells for young scientists
How do you heal when you cut your skin or break a bone? How does your body keep making new blood or brain cells, or even second teeth? How does a plant keep growing larger? The answers lie in stem cells, which are found in every growing plant and animal. Keeping the subject simple enough for young readers, a pioneer of stem cell research explains cells, tissues, normal growth, what can go wrong, and how to fix it. View Details
Stem Cells: A Very Short Introduction
by Jonathan Slack (Author)
Embryonic stem cells have been hot-button topics in recent years, generating intense public interest as well as much confusion and misinformation. In this Very Short Introduction, leading authority Jonathan Slack offers a clear and informative overview of stem cells--what they are, what scientists do with them, what stem cell therapies are available today, and how they might be used in the future. Slack explains the difference between embryonic stem cells, which exist only in laboratory cultures, and tissue-specific stem cells, which exist in our bodies, and he discusses how... View Details
Stem Cells: A Short Course
by Rob Burgess (Author)
Stem Cells: A Short Course is a comprehensive text for students delving into the rapidly evolving discipline of stem cell research. Comprised of eight chapters, the text addresses all of the major facets and disciplines related to stem cell biology and research. A brief history of stem cell research serves as an introduction, followed by coverage of stem cell fundamentals; chapters then explore embryonic and fetal amniotic stem cells, adult stem cells, nuclear reprogramming, and cancer stem cells. The book concludes with chapters on stem cell applications, including the role of stem... View Details
The Stem Cell Secret: How to Activate and Regerate Your Stem Cells Naturally and Affordably
Stem Cells live in every cell in your entire body and are designed to repair and rejuvenate your organs and tissues. Our Stem Cells become less effective in healing over time and at times can become overwhelmed with disease. This book shows how to use nutrition, supplements and life style tips to activate your Stem Cells and allow them to heal your body. View Details
Essentials of Stem Cell Biology, Third Edition
by Robert Lanza (Editor), Anthony Atala (Editor)
First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists, researchers, practitioners, and students embracing the latest advances in stem cells. Representing the combined effort of 7 editors and more than 200 scholars and scientists whose pioneering work has defined our understanding of stem cells, this book combines the prerequisites for a general understanding of adult and embryonic stem cells with a presentation by the world's experts of the latest... View Details
Stem Cells: Promise and Reality
by Lygia V Pereira (Author)
Stem Cells: Promises and Reality will tell you everything you have always wanted to know about stem cells, but could not understand the field from elsewhere. Stem cells are the great therapeutic promise of the century, and this evolving field of research and medicine brings with it many legal, ethical and psychological issues that must be discussed by society as a whole. Written so as to be accessible to general readers as well as specialists, this book explains what stem cells are, and the different aspects of stem cell research and applications. The book will enable the reader to understand... View Details