Scientists Identify Stem Cells As Hidden Cause of Cancer
© 2003 by Ralph W. Moss, PhD
Earlier this month, University of Michigan
(U-M) scientists revealed that a malignant form of stem cells
may be responsible for the development of breast cancer. According
to a U-M press release, this new understanding is "a paradigm
shift in cancer research," and the University has promised to
raise $12 million to further explore this concept.
The Ann Arbor researchers discovered that not all cells in a tumor
are equally malignant. Only a tiny minority of tumor cells are
actually capable of inducing new cancers; the rest are relatively
harmless. "These tumor-inducing cells have many of the properties
of stem cells," said Michael F. Clarke, MD, a professor of
internal medicine, who directed the study. "They make copies of
themselves --a process called self-renewal --and produce all the
other kinds of cells in the original tumor."
The University of Michigan team isolated the tumor-inducing cells
from breast cancers, both primary and metastatic, which had been
removed from nine women who were treated at the University's
Comprehensive Cancer Center. Similar cancer-causing stem cells have
previously been identified in leukemia
(cancer of the blood), but these are the first such cancer
stem cells to be found in solid tumors.
The discovery was first announced in February in the online edition
of the Proceedings of the National Academy of Sciences
(PNAS) and has now been published
in the print version of that prestigious journal. The existence of
this highly malignant subset of cells may explain why current
treatments for metastatic breast cancer often fail, according to Max
S. Wicha, MD, an oncologist and director of the University of
Michigan Comprehensive Cancer Center, as quoted in the press
release.
"The goal of all our existing therapies has been to kill as many
cells within the tumor as possible," said Wicha. But this study
"suggests that the current model may not be getting us anywhere,
because we have been targeting the wrong cells with the wrong
treatments."
"As few as 100 to 200 of these tumor-inducing cells, isolated
from eight of nine tumors in the study, easily induced tumors in
mice, while tens of thousands of the other cancer cells from the
original tumor failed to do so," Dr. Clarke said. This shows
that truly malignant cells are like the proverbial needle in a
haystack in the cancer. In the light of these findings, strategies
that aim at simply shrinking tumors with radiation or chemotherapy
are doomed to failure. They are based on an erroneous understanding
of cancer, since size alone is not critical. What is important is
killing or restricting these active cancer stem cells.
"[W]e need to develop drugs targeted at the tumor's stem cells,"
says Dr. Wicha. "If we are to have any real cures in advanced
breast cancer, it will be absolutely necessary to eliminate these
cells. What this means for women with cancer is that, for the first
time, we can define what we believe are the important cells, the
cells which determine whether the cancer will come back or be cured,"
Wicha adds. "Before this, we didn't even know there were such
cells."
Cell Surface Markers
"Cancer cells have a unique pattern of surface markers on
their outer membranes," explained Muhammad Al-Hajj, PhD, a
post-doctoral fellow who is first author of the paper. He has
compared these surface markers to a person's unique fingerprints. In
this experiment, he and his fellow scientists isolated particular
sub-populations of cancer cells and then injected these into
immune-deficient mice, a standard laboratory technique. These mice
were then examined for tumor growth every week for up to six months.
Dr. Al-Hajj found that only a small minority of cells from each
tumor were capable of causing new cancers in mice. These really
malignant cells had a unique configuration of surface markers: all
expressed a protein marker called CD44, in addition to having either
very low levels, or no levels, of another marker called CD24.
The fact that tumor-inducing stem cells from eight out of nine women
showed a common surface marker pattern is significant, Dr. Wicha
explained. "Even though it's only nine patients, it shows that
the markers identifying these stem cells were expressed in the
majority of breast cancer patients in the study. This may not be the
only expression pattern on every patient's stem cells, but it
demonstrates the validity of the cancer stem cell model."
The scientists repeated their experiment four times, just to be
sure. First, 200 cells with the unique surface pattern were isolated
from the original human tumor. After these cells produced a breast
tumor in a mouse, Dr. Al-Hajj removed that mouse tumor and used
similar techniques to then isolate 200 more stem cells from it.
These cells were then injected into another mouse to produce yet
another tumor. Once again, that mouse tumor was harvested, malignant
stem cells were separated from it, and injected into another mouse.
Each such procedure is called a passage. "When we examined the
tumors after each passage, we found their cell diversity to be the
same as the original tumor," he added.
Drs. Wicha and Clarke believe that it is likely that similar cells
drive the development of other types of cancer, as well. "What we
are working on now is finding out what makes these tumor stem cells
different from the other cells in a tumor," Dr. Wicha said.
Link to Dr. Beard
Last summer, I pointed out in this newsletter that the origin of
cancer in the transformation of stem cells was a development
anticipated one hundred years ago by John Beard, PhD. Beard
(pictured right), a
Professor of Embryology at the University of Edinburgh, Scotland,
suggested in a July, 1902 article in The Lancet that cancers arose
from 'germ cells' that were left behind in bodily
(somatic) tissue during the process
of embryo formation. He wasn't just hypothesizing. Using the
microscope, he had identified these left-behind embryonic germ cells
in the tissues of various experimental animals.
To appreciate the full significance of Beard's theory, it is
necessary to understand a little about the early stages of embryonic
development. In the very first days of its development, the
fertilized egg (called a zygote)
cleaves into two cells, which then yield four, then eight. On
or about the third day, this pre-embryo becomes a solid little ball
of cells called a morula (Latin for
mulberry, which it resembles). By the fourth day,
this morula becomes a hollow fluid-filled ball called a blastocyst.
In the interior of this ball is the inner cell mass, which will
eventually become the embryo. But surrounding this mass are
specialized cells called trophoblasts, which are ultimately destined
to become the placenta. On the sixth day or so, the whole blastocyst
burrows its way into the endometrial lining of the mother's uterus
by the invasive action of the trophoblasts. In absolute terms,
trophoblasts literally make mammalian life possible, since without
them the placenta could not form and the blastocyst could never
imbed itself into the wall of the uterus.
(It is an extraordinary irony that while trophoblasts enable the
fetus to establish itself and to grow to term, these same cells,
when they grow at the wrong time and in the wrong place, are
responsible for deadly forms of cancer. More about this in next
week's newsletter.)
Beard was the first to draw attention to the fact that trophoblasts
were virtually identical to cancer cells: invasive, corrosive and
metastatic. Other similarities between the trophoblasts and cancer
have emerged over the past few decades. For example, trophoblasts
produce a hormone known as human chorionic gonadotropin
(hCG), which has become the
standard biochemical marker of pregnancy. Academic medicine
universally acknowledges the origin of a few cancers in germ cells,
and recognizes the fact that these and some other cancers produce
hCG. However, in the late 1990s Hernan Acevedo, PhD, of Allegheny
General Hospital in Pittsburgh, PA, showed that in fact every sample
of cancer that he analyzed contained either the beta subunit of hCG
or fragments thereof. His discovery was published in the prestigious
journal Cancer, and was hailed (by the late
Prof. William Regelson) as the discovery of a "definitive
cancer marker." But it did not trigger a long-overdue
examination of the relationship between trophoblast and cancer.
(NEXT WEEK: I shall continue my
discussion of this important finding with an explanation of its
implications for cancer treatment. References will be given at that
time.)
--Ralph W. Moss, Ph.D.
If you are interested in learning about the
best currently available conventional and alternative treatments for
breast cancer, or other kinds of cancer, please consider buying one
of our detailed Moss Reports. Call us at
1-800-980-1234 or visit our website at
www.cancerdecisions.com.
**NOTE** To view this page in a more printable format, please
CLICK HERE.
IMPORTANT DISCLAIMER
The news and other items in this newsletter
are intended for informational purposes only. Nothing in this
newsletter is intended to be a substitute for professional medical
advice.
 |
|
CancerDecisions®
PO Box 1076, Lemont, PA 16851
Phone Toll Free: 800-980-1234 | Fax:
814-238-5865
Copyright © 1996-2003 All Rights
Reserved |
|
|
