Mary is a 46-year-old mother
of two daughters, ages 17 and 19. Eight years ago she was
diagnosed with breast cancer, and after a conventional course of
chemotherapy followed by radiation, the cancer was driven into
remission. Lately she is having increasingly severe back pains.
At a routine check-up, she mentions the pains to her surgeon,
who performs a bone scan. The scan reveals several "hot spots,"
regions of increased
metabolic activity in her spinal column.
The diagnosis made on a
of one of these hot spots catches
her completely off guard: metastasis of her breast cancer.
Note that the original cancer was never
but "driven into
remission." The word
"cure" is hardly ever used in relation to cancer because it is
so common for what happened to Mary to happen to anyone.
You get cancer, there is some treatment, there is then no
further trace of the cancer, but it is still there, spreading,
even if only slowly, until it shows up in some different place.
The PET scan referenced in my note above can "see" something
only as big as about five millimeters. A few cancer
carrying cells would be much, much smaller than five
millimeters. Cancer grows quite slowly when it starts, so
there can be this spreading from a tiny beginning, not
discovered for years, even.
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Patients like Mary inevitably
ask the question: Why me? But for those of us who study what
cancer is, its development and spread, the question is rather:
Why at all?
Here is where these authors show their "true colors." I consider
radicals" to be the sole cause of cancer, yet these authors
do not even mention the words. It is common for scientists
to use the grammatical "passive
voice" of a verb to hide the causative agent.
So, below, the
authors say that the
"cells become disorganized."
The verb in green here is
in the passive voice and hides from the reader what exactly is
CAUSING this "disorganization." Thus, typical of most
science, paid for by drug companies, or where the authors are
looking for drug company jobs or grants, they have learned to
NEVER touch on that which the drug companies cannot touch!
No drug can remove or neutralize "free radicals," so the drug
companies don't want to hear about them.
answer is that in cancer the genes and
chromosomes of cells
become disorganized, leading them to enact
genetic programs far
different from the intended normal program. It has often been
noted that cancer cells are unusual because they are
undifferentiated; that is, they lose functions and, as a result,
fail to fully develop the characteristics and proper activities
of mature cells of their type. Quite remarkably,
cancer cells gain new functions, taking on characteristics
unrelated to the normal, often sedentary cell type.
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Most cells are designed to
remain fixed in their organs in order to perform the specialized
activities for which they are particularly adapted. They are
held tightly in place by
molecular tethers that link them with
the other cells and the
proteinaceous matrix in that tissue.
Clearly, these cells are not meant to roam around the body and
take up residence in other organs. Metastatic cancer cells are
altered in such a way that they can break those bonds. Further
cellular remodeling allows metastatic cells to chew through the
proteinaceous walls that line tissues and blood vessels and
quite literally walk away from their parent organ to invade
other tissues and organs.
This is rather far-out stuff. Here is yet another "Greek
language" explanation of this word "tether" and how it applies
The major barrier for
invading tumour cells, migrating leukocytes, and growing blood
vessels (endothelial cells) is the basement membrane (BM) that
surrounds the vessels, and the extracellular matrix (ECM)
which forms a scaffold in tissues to hold cells together.
The BM and ECM are
composed of an interlocking network of proteins and complex
carbohydrates, and for cells to breach this barrier, they
deploy a battery of enzymes that break down these proteins and
The major carbohydrate is
heparan sulphate (HS), which acts as the glue to maintain the
integrity of the BM and ECM. The enzyme responsible for
cleaving HS, heparanase, has been shown to play a key role in
the degradation of the BM and ECM, and its activity strongly
correlates with the metastatic capacity of tumour cells and
the migratory capacity of leukocytes and endothelial cells.
HS in the ECM also
binds a number of angiogenic growth factors, and the release
of these by heparanase promotes angiogenesis and tumour
growth. Following our recent cloning of mammalian heparanase,
we have been able to develop the tools to investigate how
heparanase functions at the molecular level and to directly
determine the role of heparanase in cell invasion,
angiogenesis and inflammation. (source)
You can take
from the above, in simple terms, that cancer normally starts in
normal cells, and most cells are fixed in place by something
called "tethers" or "bindings." When a cancer cell starts
growing beyond the size and supply of nourishment (mostly sugar)
it demonstrates a very strong urge to "survive" and so it works
to "break loose" from its restrictive area and "move" to a new
location. This may not be scientific, but it is probably
helpful in understanding the process.
scientists who wrote this article MUST have known about the
generally secret research being done (in the open, but not
publicized) which has "exactly" spotted the cause of the
"breaking loose" and the "eating through" the shell that
surrounds the cancer. If you want the full story, and have
the time to study, you'll be spending many hours on these pages!
If it were not so potentially
damaging, metastasis might be just an interesting cellular
oddity. But the fact is that the metastatic tumor is often more
dangerous than the original, or primary, tumor. Metastatic
cancer cells crowd out normal cells in the tissue and deprive
them of nutrients. In effect, the metastatic cells starve and
displace functional cells. This can be lethal when the organ—or
organs, since cancer cells can go almost anywhere and often end
up in several new organs—can no longer perform its vital
Over the past few decades,
biologists have become ever more precise in determining the
genetic, biochemical and cellular changes that drive a cell
first to become cancerous and
then to become metastatic.
discoveries are being reported daily. So, although not all of
the details are entirely known, a comprehensive picture of these
alterations is emerging. Each new piece of information not only
contributes to this overall picture; it also provides a site of
potential therapeutic intervention to inhibit the progression of
cancer—if not, someday, to eliminate it entirely.
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A diagnosis of cancer marks an
abrupt change in the life of the patient. A line of demarcation
has been drawn. Life seems to be separated into before and
after. Yet the events that lead a cell to become cancerous take
place gradually, sometimes over periods that can exceed 10
years. During this lengthy evolution, cells undergoing cancerous
transformation accumulate genetic abnormalities, one important
consequence of which is that cellular growth becomes
This is important, even vital, data. More people need to
realize that they should be living a life style that PREVENTS
cancer, not wait until 10 years of slow growth springs upon
them! Amazingly "chelation
therapy," particularly "oral chelation therapy" has a tremendous
success record on this line.
The number of cells in normal
tissue is strictly controlled by a system of checks and
balances. Cells that are too old, that fail to function properly
or that are otherwise no longer needed are programmed to die, a
process known as apoptosis. These cells are replaced by
new cells, derived from primitive precursors, also called
stem cells, that divide and then differentiate into the
mature cell type that performs a specific function. In time,
these too undergo apoptosis, only to be replaced by younger
Cell death does not take place
because a cell just falls apart. Rather it is the result of a
carefully controlled genetic program. Given the proper signals,
particular genes are activated that encode proteins that carry
out the cellular suicide.
Note: This author has said it, but it is worth repeating -- what
a fascinating thing it is for a free radical to CHANGE a cell so
that it "lives longer" than it should! This could be a
clear philosophical signal that "death" has a vital role to play
Not all cells undergo
apoptosis. There is, in fact, a striking variation in the
longevity of different cell types. Nerve and muscle cells, for
example, are extremely long-lived—if all goes well, they endure
for the entire life of the individual. Once these cells reach
their fully mature state they can no longer divide, and it is
unlikely that there are populations of stem cells that can
generate replacements when they die.
Other cells are actually
designed to die shortly after reaching maturity. Often these are
the cells that turn over frequently, such as skin cells, or the
epithelial lining of the digestive system. The epithelial cells
lining the digestive tract mucosa live for a maximum of four
days after reaching maturity. High-turnover tissues are endowed
with a population of stem cells ready to replenish their
respective tissues with mature cells, as older cells are
sloughed off, used up or eliminated. For example, stem cells in
the bone marrow divide continuously to provide sufficient
numbers of blood cells. Similarly, the stem cells in the
digestive tract are constantly dividing to replace worn-out
mucosal epithelial cells.
Some tissues maintain
cell-growth rates intermediate between these two extreme
scenarios. For example, under normal circumstances, cell
division in the liver takes place at a very low rate: At any
given time, only one in 10,000 liver cells is dividing. But
cell-division rates can be driven up when needed, for instance,
to replace cells damaged by viral infection or removed by
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Clearly, then, maintaining the
proper number of cells in any tissue requires a delicate balance
between cellular production and elimination. Essential to this
balance is apoptotic cell loss on one hand and cell division on
the other. When an excess of cells is produced by unrestrained
cell division, or when too few cells are eliminated by
apoptosis, an overabundance of cells accumulates in the tissue.
This basically describes the situation in cancer.
As with all cellular
functions, a cell's life and death are under strict genetic
control. These genes encode proteins that sense growth signals
from the environment, or drive the cell through its
cycle and check for cellular and genetic abnormalities. Some of
these regulatory proteins make the necessary corrections to
damaged genes. Other proteins direct the cell to exit the cell
cycle in order to differentiate. Still other proteins remove old
or defective cells from the replicative cycle and send them
en route to apoptosis.
It stands to reason that if
any of these genes or the proteins they encode become faulty,
the cell-division cycle will become abnormal.
Again, note the "careful" absence of any reference to a
causative agent -- such as the free radical!
alterations to the series of proteins that detects external
growth cues can lead to an abnormally prolonged growth cue.
Problems with the proteins that regulate the cell cycle can,
likewise, maintain cells in a
normally would exit the cycle and start to differentiate and
In recent years, scientists
have found that in the majority of cancer cells, one or several
of these growth-regulatory genes is either missing or defective.
It should be noted that all of these genes, when functioning
properly, are crucial in maintaining the normal growth
characteristics for each cell type. These genes only promote
cancer when they become mutated or altered.
Again, how amazing that the simple fact that a cell can "be
missing or defective" is written without a thought of causation.
Surely a true scientist would wonder, "Why!" Can they not
at least look at the possibility that a free radical could, and
actually does, cause this damage?
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Cells on their way to becoming
cancerous accumulate a number of genetic and chromosomal
abnormalities, each of which in some way pushes the cell further
in the direction of unrestricted growth. At first, clusters of
genetically identical cells are formed, each cell dividing with
less restraint than its normal neighbors. This cluster does not
at this point constitute a tumor.
When the cell mass attains a
diameter of about 2 millimeters, the cells emit signals that
recruit surrounding connective tissue and vascular cells to the
tumor and induce them to grow into blood vessels.
Realize that the PET scan can only see something as big as 5 mm,
so these cancerous beginnings are NOT seen with the usual tests.
When a cell mass starts creating its own "blood vessel system"
within it, that is the preparing for the time when the usual
body supply of blood won't reach these cells. At this
point the mass of cells is still depending on the oxygen in the
blood for life. That soon changes!
The cell mass
literally stimulates the growth of its own blood supply from
existing blood vessels, a process called angiogenesis.
This term become popular when "shark cartilage" started to be the
item to prevent cancer. That was because it was "found"
that sharks never got cancer, it was also realized that sharks
did not have "bones," but had cartilage and that there was
something about shark cartilage which prevented this action of
There is some evidence that angiogenesis is probably initiated
because cells in the mass, especially those in the interior,
become starved for oxygen. In any event, once the blood supply
is in place, the cell mass can import oxygen and the nutrients
it needs to keep growing. Furthermore, the cells now have a
conduit through which they can escape and invade other tissues.
Angiogenesis seems to have an additional consequence. Connective
tissue surrounding blood vessels release factors (as do the
vascular cells) that stimulate the growth and motility of cancer
cells. Strange as this may sound, cancer can only develop if the
cancer cells are adequately supported by host tissues.
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The escape of cancer cells is
not a trivial matter. As mentioned above, most normal cells are
tightly hooked in place by chemical bonds linking them to
neighboring cells, to the surrounding
matrix—the mortar of tissues—or both. This is especially true of
epithelial cells that line many organs and from which the
majority of cancers arise. The cells are held in place by large
molecules on their surfaces that connect with similar proteins
on neighboring cells or with proteins in the matrix. In addition
to these molecular tethers, most normal cells simply lack the
migratory machinery of mobile cells.
"matrix" used here assumes vital importance, much more than
given by these authors. If this "matrix" degrades, it
loses its ability to hold things together. So, the body
can produce "matrix degradation inhibitors!"
"inhibit" the "degradation" of the "matrix." That is
astounding -- it is central to all cancer research and
treatment, but not allowed into the public arena.
special forms of enzymes, made, of course, from protein, but the
special thing about these enzymes is that they don't exist
without an atom of METAL in the molecule! This is well
accepted, but little known!
allows these enzymes to function to INHIBIT the destruction or
"degradation" of the matrix. When that metal atom, which
MUST be there for the enzyme to work, -- when that metal atom
changes to a free radical, THEN the enzyme is no longer capable
of protecting the matrix. The matrix "degrades" and the
cancer cells break free -- to spread. This is the truth
that is being deliberately kept from you by drug companies who
haven't figured out yet how to do something about that "metal
atom, free radical" with a drug!
be done about it with oral chelation! But, you won't catch the
drug companies admitting that!
There are, of course, some
important exceptions, most notably the white blood cells that
constitute the immune system. These are designed to migrate out
of the blood stream and into tissues to fight infection. In
order for sedentary cells to metastasize, they must lose their
adhesive connections and take on the migratory properties
usually restricted to white-blood cells.
Do not miss the important information and explanation of the
image by clicking on the image of the white blood cell.
The text which
follows is FULL of technical references which I have NOT tried
to explain further. You can read this type of stuff and
simply realize that there are activities going on within a cell
that you can appreciate without understanding. Don't
click for full image
Figure 3. Cycle of events leading to cell division is under strict
genetic control. Resting cells are in the phase called Gap0
During this period cells cannot divide, but
they can differentiate by maturing and taking on the
functions of the mature cell type.
When cells receive
external cues to divide they enter the cycle at the Gap1
During G1, cells
manufacture cellular components, such as RNA and proteins,
in preparation for division.
After a time, the cells enter
the Synthesis (S) phase in which the cell's DNA is
During the next phase, Gap2 (G2),
the cell continues to manufacture proteins and RNA.
the cell undergoes Mitosis (M), during which each daughter
cell receives a complete set of the cell’s genes, along with
all of the other constituents it needs to function and
To ensure that cell division equals
loss the cell’s response to growth cues is regulated, for
example, by the protein Myc, encoded by the gene c-myc,
which exerts its effects during the G1 phase of
In order that DNA be faithfully duplicated,
checkpoints exist at certain steps of the cell cycle. The
p53 protein mediates a checkpoint when the cell enters the S
If all is well, the cell continues with the cycle.
But if the DNA is damaged, the cell cycle is stopped to
allow for DNA repair.
If the damage is so severe that it
cannot be fixed, the cell exits the cycle and instead
Mutations in the c-myc gene, in the p53
gene or in any of the many other regulatory genes, or the
genes that encode proteins that correct defects in DNA,
alter the cell cycle. Alterations lead the cell to proceed
through the cell cycle with damaged DNA, which contributes
to the kinds of chromosomal anomalies seen in Figure 2.
Again these authors talk about "mutations" without ever even
breathing the words "free radicals." It is impossible to
understand cancer fully without understanding "free radicals."
Perhaps another reason why they don't mention "free radicals" is
that they know that both chemotherapy and radiation are designed
to CREATE free radicals in your body, and that free radicals are
killers. Any alternative cancer therapy that does
NOT explain ITS role in handling free radicals may "work" but
doesn't have the type of full explanation that science is
capable of providing.
These in turn lead to further deregulation of the cell cycle
such that cellular proliferation is excessive, and apoptosis
reduced. The net effect is an overabundance of cells, which
is basically the situation in cancer.
Sticking Together, Coming Apart
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The impact of cellular
adhesion in cancer is most clearly manifest in carcinomas—cancers
of epithelial cells.
Epithelial cells exhibit a rich variety of
molecular interconnections. One of these is a very specific
cell-membrane structure called the adherence junction.
If you want more technical data about these "junctions," read
here and click for the source.
to understand the molecular mechanisms that enable epithelial
cells to bind to each other in order to form an impermeable
barrier," said Valeri Vasioukhin, Ph.D., a postdoctoral fellow
in the lab of Elaine Fuchs, Ph.D., Amgen Professor of
molecular genetics & cell biology and biochemistry & molecular
biology. Fuchs is an expert on epithelial cells and skin
Primarily responsible for the junction is E-cadherin, a large
protein that spans the membrane such that one end of the protein
pokes out of the cell's surface, while the other end projects
into the cell's interior. The external portion of E-cadherin
forms interlocking bonds--like the teeth of a zipper—with E-cadherin
molecules on neighboring cells. The internal portion hooks into
the cell's interior protein skeleton, called the
cytoskeleton. Recently, the proteins linking E-cadherin
molecules to the cytoskeleton have been identified. These
proteins are called catenins.
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Before a cell can even start
to move about, it first must break this complex,
multidimensional interlocking structure. The adherence junction
must be disassembled. This might be achieved in one of three
First, an alteration
[notice the absent reference to free
radicals] in the structure of E-cadherin could
be introduced that would prohibit it from forming proper
connections. [This would be a change that
inhibits matrix function, or a change which CREATES something
that destroys the matrix!] Such an alteration would imply that the gene
encoding E-cadherin had become mutated, corrupted in such a way
that it encoded a less functional or even a nonfunctional
protein. Surprisingly, mutations in the E-cadherin gene are
Second, there could be a
decrease in the number of E-cadherin molecules on the cell
surface. And, indeed, studies have shown that this is the case
in many cancer cells.
actually shown is that there are SOME of these molecules that
contain free radical forms of the metal which is an essential
part of these molecules. There are also OTHER molecules where
the atom of metal in it is NOT in a free radical form. The
same means of testing might not detect both types! In any
event, when the proportion of these molecules with free radicals
atoms of metal start exceeding the molecules which are "normal,"
you have trouble.!
Finally, the linking proteins—the catenins—might
be absent or nonfunctioning. This has in fact been found in an
increasing number of cancers. The breakdown of cellular
junctions not only diminishes the connections between epithelial
cells, but it is also related to the cell's increasing internal
radicals are at the heart of this problem, and are deliberatly,
or ignorantly, overlooked by these authors!]
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It has long been noted that
the internal architecture of cancer cells is irregular and
disorganized. In general, E-cadherin expression is closely
related to cellular differentiation. When they do occur,
mutations in the E-cadherin gene often result in poorly
differentiated cancer cells whose internal architecture no
longer resembles the original structure. Furthermore, the lack
of E-cadherin expression alters the relation of cells to each
other. The same holds true for catenin mutations.
Of the three forms of catenin
molecule, β-catenin has received the most attention. Work in the
Johns Hopkins laboratory of Bert Vogelstein has shown that β-catenin
not only helps to maintain tissue architecture, it also
participates in the cell's internal chemical signaling system.
Normally, β-catenin hooks up with another protein called APC
(for adenomatous poliposis coli), whose function is to eliminate
cells with mutations via apoptosis. A mutation in the APC
protein leads to the growth of polyps, small benign tumors in
the colon. For people who inherit mutations in APC, the risk is
rather large that these polyps will become cancerous.
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When acting alone, β-catenin
has the potential to initiate cell division. The complex of β-catenin
bound to APC prevents this from happening. In this way, cell
growth is inhibited. Sometimes one or the other of the proteins
in this complex becomes altered—owing to a mutation in the genes
encoding them—and the complex cannot be formed. In that case, β-catenin,
now unrestrained by APC, interacts with the cell's DNA and
activates several genes that cause the cell to re-enter the cell
cycle. Abnormal cell growth ensues.
Just as E-cadherins link cells
to one another, molecules called
integrins link cells
to proteins such as collagen in the surrounding connective
tissue. Like E-cadherin, the integrins span the cell's membrane,
forming connections with connective-tissue proteins outside the
cell as well as with proteins in the cell's cytoskeleton, inside
the cell. One important difference between normal and cancer
cells on the brink of metastasizing is that the cancer cells
produce fewer integrins capable of linking with connective
tissue than do the normal cells.
Researchers very quickly picked up
on the fact that this test not only gave a patient's outcome.
But blocking of integrins could also be used to fight cancer.
The intergin seems to act on a
molecular level and can encode the DNA and allow angiogenesis
to occur in that manner. What they used in the test to block
the integrin was a cyclic peptide intravenously. The results
showed "regression of human tumors transplanted onto chick
cloriallantoic membrane." (source)
As long as tumor cells continue to
need oxygen to survive, we have a chance to knock cancerous
tumors out. (source)
A review of published
information fails to support a cancer-causing or
growth-enhancing effect by Hyperbaric Oxygen Treatment. (Source)
Interestingly, not all
integrin synthesis stops. On the contrary: In cancer cells
integrins are still being produced, but these constitute a set
of integrin proteins different from those on normal cells. The
so-called invasive cells on their way to becoming metastatic
produce integrins that seem to help them migrate through the
connective tissue or blood-vessel wall. Specifically, the
migratory cells extend cytoplasmic protrusions (like the
pseudopods of an amoeba) into the matrix of connective tissue.
These protrusions latch on to proteins in the matrix with the
help of the new integrin molecules and pull themselves through.
What a wonderful missed opportunity these people had to mention
whether or not "oxygen" might have any effect on this situation.
If you are trying to get data about "oxygen therapy" you won't
find it here where it could have and should have been.
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In order for a cell to make
protrusions, its cytoskeleton has to be configured for motility.
But as already noted, most cancer cells start out as sedentary
cells and are neither programmed genetically for motility, nor
is their basic skeletal structure conducive to it.
cancer cell can walk away from an organ, its cellular skeleton
must be restructured for movement. And it is. The idea that a
cell can alter its internal architecture is akin to suggesting
that a fish can grow leg bones and walk off. And yet, biologists
have long observed that cells do in fact change shape through
the course of cancerous transformation.
In their normal state,
epithelial cells come in several shapes—cylindrical, cuboid or
Their cancerous counterparts become somewhat
star-shaped and elongated and more closely resemble fibroblasts
than they do epithelial cells. (Fibroblasts are the cells in the
connective tissue that form a wall around epithelia and produce
the matrix of connective-tissue proteins.)
similar fibroblastic morphology is also observed in epithelial
cells during embryonal development. This raises the interesting
point that many characteristics of tumor cells resemble those
normally seen only during the very early stages of embryonic
The internal cell structure is
not the only thing that must be remodeled before the metastatic
cell can leave its host organ. The matrix of proteins forming
the connective tissue is like a wall without doors. Somehow, the
metastatic cells must pass through this wall. This means that
either the wall must be altered, or the cancer cells must
acquire the ability to bore through tissue.
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The latter scenario seems to
take place. Cancer cells penetrate and pass through this barrier
by dissolving it.
misleading this is -- as if the causative agent is an evil
cancer cell. The true cause is a free radical (possibly from
cigarette smoke?) that changes the atom in the middle of this
enzyme to be a free radical, thus changes the function of the
molecule, and damages the matrix which had been holding the
cancer cells "in place."
For this purpose, cancer cells use
proteases, enzymes that break down proteins, to degrade the
mortar of the connective-tissue wall.
misleading. The cancer cells are not "using" anything --
but rather the person has been living a life style that
increases the number of free radiclas in his body -- some of
them cause changes in the molecule that inibits the degradation
of the matrix!
It is probable that
expression of active proteases is precisely coordinated in time
as well as in extracellular location. For example, fibroblasts
produce and degrade the matrix continuously, and under normal
circumstances, this process is in equilibrium with other factors
that rebuild the matrix. At the moment, it is not entirely clear
whether the cancer cell releases its own proteases, or whether
it stimulates protease release from other cells, or whether both
processes take place sequentially or simultaneously. What is
known is that certain messenger molecules alter the balance. It
is possible that cancer cells have acquired the ability to
synthesize these messenger molecules.
[No matter HOW
this happens, the action is through the operation of a free
radical -- drugs do not reduce free radicals, but increase them.
Oral chelation removes the metals that are free radicals, and
which create more free radicals.
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All proteases share a common
feature: They are synthesized by cells in an inactive form,
which must be chemically processed before they become active.
Processing requires other proteases to chew away at a portion of
the precursor protein, called a proprotein, in order to expose
the active site of the protease. Complicating the balance is the
fact that cells producing proteases may also produce natural
protease inhibitors. Sometimes, chemicals in the environment can
inhibit the protease inhibitors.
[Such a vital
comment -- hidden in obscurity here! Yes, there are
"chemicals in the environment can inhibit the protease
inhibitors" but why not admit that these "chemicals" are free
So, the ability of a cancer
cell to pass through its host tissue depends on some
constellation of events that either promotes the synthesis
and/or the activation of proteases or prohibits protease
inhibition. The net effect is that proteases chew through the
connective tissue, allowing the metastatic cancer cells to pass
through. (Proteases secreted by endothelial cells may play a
role in the angiogenesis required for the growth and metastasis
of the primary tumor.)
for the remainder of this article.