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Imagine a healthy tissue containing thousands of cells.
Each cell serves the greater good, which is the continuation
of a person’s life. Each cell is programmed so that
when the cell is old or no longer needed, it dies a peaceful
and timely death. This death is called apoptosis. All
cells are in communication, which allows for the smooth
repair and replacement of tissues and other aspects of
cell behavior. Communication takes place either indirectly,
via exchange of messenger compounds such as
hormones and growth factors, or directly, via cell-to-cell
contact. Contact allows cells to respond to the “feel” of
neighboring cells, via cell adhesion molecules, and to
exchange messenger molecules through cell-to-cell portals
called gap junctions. With the help of proper communication,
appropriate cells proliferate when new cells
are needed, and when enough new cells have been produced,
cell division stops.
Cancer cells are the descendants of a normal cell in
which something has gone wrong. In this normal cell,
some kind of internal or external stress causes a mix-up
in its genetic code (its DNA). This event is said to “initiate”
the cell to a precancerous state. After its DNA has
been damaged, the cell withdraws from close communication
with its neighboring cells. Interrupted cell-to-cell
communication is a common result of DNA damage or
other forms of cellular damage. Separated from the
regulatory controls of its community, it is now at the
mercy of its environment. Let us say that the environment
around this cell contains a promoting agent, which
is a compound that stimulates cell proliferation. In response
to the promoting agent, this precancerous cell
divides to produce daughter cells, and these daughter
cells divide to produce more daughter cells, and so on.
All are proliferating only in response to the promoting
agent. The promoting agent may be a chemical foreign
to the body, or it could come from a natural process such
as inflammation. One day, the worst occurs. The genetic
instabilities passed down through the generations
finally result in one cell that becomes capable of selfstimulation,
and on this day an autonomous cancer cell
is born. This cell no longer requires the promoting
agent to stimulate its proliferation. The role of the promoting
agent is made obsolete by the cell’s ability to
make proteins such as growth factors that stimulate proliferation.
This original cancer cell divides to produce daughter
cells, these cells also divide, and soon there is a population
of cancer cells. As they divide, they develop malignant
characteristics, such as the ability to invade and
metastasize. They also develop other characteristics that
help assure survival, for example, the ability to evade
the immune system, to mutate when faced with adverse
conditions, and to induce the growth of new blood vessels
through the process called angiogenesis. The development
of these characteristics marks the third stage
in carcinogenesis, the first two stages being initiation
and promotion, respectively. I use the term
progression to refer to both the third stage of carcinogenesis
proper and to the entire postpromotion period of
the cancer’s life. This correctly implies that progression
is an ongoing, evolving process.
Compared to normal cells, cancer cells have lost touch
with their neighboring cells, their community purpose,
and even largely with one another. They are a race of
self-serving, easily adaptable cells, whose proliferation
continues with the slightest provocation. They use more
than their fair share of resources, live longer than their
fair share of time, and produce more than their share of
offspring. In short, they exhibit the two deadly characteristics
of cancer: uncontrolled proliferation and uncontrolled
spread. |