Technique Developed At Stanford Enables Creation Of Cancer Stem Cells
Article Date: 10 Apr 2008 - 4:00 PDT
With a bit of genetic trickery, researchers at the Stanford
University School of Medicine have turned normal skin cells into
cancer stem cells, a step that will make these naturally rare cells
easier to study.
Cancer stem cells are thought to be the ones that drive a cancer, and
are therefore the targets of any cancer therapy that must kill them
in order to be effective. Understanding these cells has been a
challenge, however, because they are rare, difficult to isolate and
don't grow well in the lab.
Howard Chang, MD, PhD, assistant professor of dermatology and senior
author of the work, said being able to generate cancer stem cells
from normal cells will help move that research forward. "The upshot
is that there may be a way to directly create cancer stem cells in
the lab so you don't always have to purify these rare cells from
patients in order to study them directly," he said. The work will be
published in the April 10 issue of Cell Stem Cell.
The study also demonstrated that cancer stem cells are much more
similar to the stem cells found in embryos, which can develop to form
all tissue types, than they are to the more-restricted adult stem
cells. This finding has important implications for understanding how
cells go awry when they become cancerous.
Cancer stem cells were first discovered in 1994 by researchers at the
University of Toronto. In 2003, Michael Clarke, PhD, who was then at
the University of Michigan, discovered cancer stem cells in the first
solid tumor, breast cancer in this case, showing that the concept of
cancer stem cells wasn't restricted to blood cancers. Clarke has
since moved to Stanford, where he is the Karel H. and Avice N.
Beekhuis Professor in Cancer Biology, and Stanford has become a
leader in cancer stem cell research, with teams finding cancer stem
cells in head and neck cancer, colorectal cancer and additional blood
cancers. Laboratory researchers at the medical school are also
beginning to work with clinical groups to apply cancer stem cell
findings to patient care.
One question among cancer stem cell researchers has been how those
cells originate. "By the time a patient comes to a hospital, they
already have a cancer, so that process has already happened," Chang
said. Generating cancer stem cells in the lab gives scientists
insight into how the transformation happens and could lead to new
ways of either stopping the transformation early on or detecting and
destroying those cells once they form.
Chang and first author David Wong, MD, PhD, postdoctoral scholar,
began to answer the question of how cancer stem cells originate by
comparing genetic activity in embryonic stem cells with the activity
in normal adult stem cells. They found a large group of genes that
were active only in embryonic cells. They then looked at which genes
were active in cancer stem cells and found that the pattern resembled
that of embryonic stem cells.
The finding was a surprise, given that once embryonic stem cells
become committed to forming adult cells, such as skin, brain or
blood, they were thought to forever deactivate those embryonic genes.
Instead, Chang said this work suggests that when those adult cells
become cancerous, they turn those embryonic genes back on.
The group also noticed that the genes active in both embryonic and
cancer stem cells are controlled by a few biological master
regulators. One of those genes, called Myc, has also been shown
recently to help convert normal skin cells into embryonic-like cells.
By activating two genes in addition to Myc in normal skin cells,
those cells were transformed into what appeared to be cancer stem
cells. When transplanted into laboratory mice, the cells formed
tumors, one hallmark of a true cancer stem cell.
From here, Chang and Wong hope to learn more about how these genes
activate a cancerous state. "Our particular interest is in using this
approach to find the mechanism that turns a normal cell into a cancer
stem cell," said Chang, who is also the Kenneth G. and Elaine A.
Langone Scholar of the Damon Runyon Cancer Research Foundation.
------------
Article adapted by Medical News Today from original press release.
------------
Other Stanford researchers who contributed to this work include
medical student Helen Liu; Todd Ridky, MD, PhD, instructor in
dermatology; and David Cassarino, MD, assistant professor of
pathology.
The work was funded by grants from the National Institutes or Health,
the American Cancer Society and a Dermatology Foundation Research
Career Development Award to David Wong.
Stanford University Medical Center integrates research, medical
education and patient care at its three institutions - Stanford
University School of Medicine, Stanford Hospital & Clinics and Lucile
Packard Children's Hospital at Stanford. For more information, please
visit the Web site of the medical center's Office of Communication &
Public Affairs at http://mednews.
Source: Amy Adams
Stanford University Medical Center
http://www.medicaln
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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