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Sat, 26 Apr 2003 08:10:46 -0400 (EDT)

 

 

THE MOSS REPORTS Newsletter (04/26/03)

 

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Ralph W. Moss, Ph.D. Weekly CancerDecisions.com

Newsletter #81 04/26/03

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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, 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.

 

 

To view a picture of Dr. John Beard go to:

http://www.cancerdecisions.com/images/beard.gif

 

 

(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, PhD

 

 

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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

 

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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.

 

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