Cancer Cells: How They Start and

Characteristics
Cancer cells are cells gone wrong — in other words, they no longer respond to many of
the signals that control cellular growth and death. Cancer cells originate within tissues
and, as they grow and divide, they diverge ever further from normalcy. Over time, these
cells become increasingly resistant to the controls that maintain normal tissue — and as
a result, they divide more rapidly than their progenitors and become less dependent on
signals from other cells. Cancer cells even evade programmed cell death, despite the
fact that their multiple abnormalities would normally make them prime targets for
apoptosis. In the late stages of cancer, cells break through normal tissue boundaries
and metastasize (spread) to new sites in the body.

Normal cells become cancerous when a series of mutations leads the cell to continue to
grow and divide out of control, and, in a way, a cancer cell is a cell that has achieved a
sort of immortality. Also unlike normal cells that remain in the region where they began,
cancer cells have the ability to both invade nearby tissues and spread to distant regions
of the body. We will look at the process that leads to the development of a cancer cell,
some of the ways in which cancer cells differ from normal cells, and why the body may
not recognize cancer cells and destroy them as it does other "foreign" cells.

Pathophysiology of Cancer

How Do They Start?

Cancer cells are usually formed after a series of mutations cause them to become
increasingly abnormal. These mutations are either inherited or more often, caused by
carcinogens (cancer-causing substances) in our environment. That cancer is caused by
not one but several mutations explains why cancer is more common in older people and
why it is often multifactorial (meaning there are several factors that work together to
cause cancer) in origin. It also helps explain a genetic predisposition to cancer. A
genetic predisposition does not mean you will get cancer, but, simplistically, if a few
mutations are already in place, it will likely take fewer acquired mutations for a cell to
become cancerous.

The process of normal cells becoming cancer often goes through stages in which the
cell becomes progressively more abnormal appearing. These stages may include
hyperplasia, dysplasia, and finally cancer. You may also hear this described as
differentiation. Early on a cell may look much like normal cells of that organ or tissue,
but as progression occurs, the cell becomes increasingly undifferentiated. This is, in
fact, why sometimes the original source of cancer cannot be determined.

What Makes Them Divide and Grow

A cancer cell can have thousands of mutations, but only a certain number of these
genetic changes in cancer cells cause cancer to divide and grow. Mutations which result
in the growth of the cancer cells are referred to as "driver mutations," whereas other
mutations are considered "passenger mutations." Normal genes called proto-oncogens
can become "oncogenes" when mutated and code for proteins that drive the growth of
cancer, and give cancer its immortality. Tumor suppressor genes, in contrast, are genes
within the cell which tell cells to slow down and stop growing, repair damaged DNA, or
tell cells when to die.

Most cancer cells have mutations in both oncogenes and tumor suppressor genes
which lead to their behavior.

Types of Cancer

There are as many types of cancer cells as there are types of cancer. Of the
hundredplus types of cancer, each is named for the type of cancer cells in which it
began. Carcinomas are cancers that arise in epithelial cells that line bodily cavities.
Sarcomas are cancers that arise in mesenchymal cells in bones, muscles, blood
vessels, and other tissues. Leukemias, lymphomas, and myeloma are "blood-related
cancers" that are "fed" by nutrients in the bloodstream and lymph fluid such that they
don't need to form tumors. Just as cancers may behave differently from one another,
not all cancer cells behave the same way.
Cancer Cells vs. Normal Cells

There are many important differences between cancer cells and normal cells. Some of
these include:

 Growth: Normal cells grow as a part of growth and development such as during
childhood, or to repair injured tissue. Cancer cells continue to grow (reproduce)
even when further cells are not needed. Cancer cells also fail to listen to signals
that tell them to stop growing or commit cell suicide (apoptosis) when the cells
become old or damaged.
 Ability to invade nearby tissues: Normal cells respond to signals from other
cells which tell them they have reached a boundary. Cancer cells do not respond
to these signals and extend into nearby tissues often with finger-like projections.
This is one reason why it is difficult at times to surgically remove a cancerous
tumor. The word cancer, in fact, is derived from the Greek word carcinos for crab,
referring to these claw-like extensions into neighboring tissues.
 Ability to spread (metastasize) to other regions of the body: Normal cells
make substances called adhesion molecules that cause them to stick to nearby
cells. Cancer cells, lacking the stickiness caused by these adhesion molecules,
can break free and float to other regions of the body. They may travel to nearby
tissue, or through the bloodstream and lymphatic system to areas of the body far
from the original cancer cell—for example, a lung cancer cell may travel
(metastasize) to the lymph nodes, brain, liver, or the bones.
 Immortality: Normal cells, like humans, have a lifespan. When they reach a
certain age, they die. Cancer cells, in contrast, have developed a way to “defy”
death. On the end of our chromosomes is a structure known as a telomere.
Every time a cell divides, its telomeres become shorter. When the telomeres
become short enough, the cells die. Cancer cells have figured out a way to
restore their telomeres so that they don’t continue to shorten as the cell divides,
thus, in a way, making them immortal.
The ability to invade and metastasize is very important in differentiating a cancer cell
from a normal healthy cell, but there are many other important distinctions as well.

Cancer Cell

• May keep growing

• May invade nearby tissues
• May spread to other regions of the body
• Can be immortal

Normal Cell

• Grows when needed

• Stays within tissue boundaries
• Sticks to nearby cells
• Has defined lifespan

Why Doesn’t the Body Recognize Cancer Cells as Abnormal and

Destroy Them?

A good question is, "Why don’t our bodies recognize and remove cancer cells as they
would, say a bacteria or virus?" The answer is that most cancer cells are indeed
detected and removed by our immune systems. Cells in our immune cells called natural
killer cells have the job of finding cells that have become abnormal so that they can be
removed by other cells in our immune system. Cancer cells remain alive either by
evading detection (they disguise themselves in different ways) or by inactivating the
immune cells that come to the scene.

The ability of the immune system to recognize and eliminate cancer cells is thought to
be responsible for the uncommon but well-documented phenomena of some cancers
going away without treatment of (the spontaneous remission of cancer.) This process
also lies at the crux of the new field of cancer treatment known as immunotherapy.
Cancer Cells Keep Changing

Once a cancer has formed, the cells don't remain the same, but rather continued
mutations may occur. This, in fact, is why resistance develops to chemotherapy and
targeted therapy drugs in time. The cancer cell develops a mutation that allows it to
bypass the damaging effects of these treatments.

That cancer cells change is very important in treatment. For example, a breast cancer
that is estrogen-receptor positive may be estrogen-receptor negative when it recurs or
spreads. It also helps explain why cancer cells in different parts of a tumor may be
different. This is referred to as "heterogenicity" (containing more than one allele of a
gene —used of a cell or of population) and is important in diagnosis and treatment as
well.

How Do Cancer Cells Differ From Precancerous Cells?

Precancerous cells may look abnormal and similar to cancer cells but are distinguished
from cancer cells by their behavior. Unlike cancer cells, precancerous cells do not have
the ability to spread (metastasize) to other regions of the body.

An often confusing condition is that of carcinoma-in-situ (CIS.) Carcinoma-in-situ

consists of cells with the abnormal changes found in cancer cells, but since they have
not spread beyond their original location (or technically, have not gone beyond
something called the basement membrane,) they are not technically cancer. Since CIS
can turn into cancer, it is usually treated as early cancer.

Final Thoughts

An analogy to describe cancer cells has been that of a car. The growth of the cells can
be pictured as a car that has the accelerator stuck down. At the same time, the brakes
don’t work (the cells doesn’t respond to tumor suppressor proteins.)
We can take this analogy a step further. The invasion of cancer cells can be viewed as
a car breaking through a gate into a gated community. Normal cells respond to signals
from neighboring cells that say “this is my boundary, stay out.” Cancer cells are
antisocial in other ways as well. As they “gang” up with other cancer cells, all of which
are becoming more immature in their actions over time (due to rapid division), they
spread out and invade other communities as well.

It is actually very difficult for a normal cell to become a cancer cell. It has to be abnormal
in ways that facilitate growth, inhibit repair and death, ignore signals from neighbors,
and achieve a form of immortality. This is why cancer isn’t caused by a single mutation,
but rather by a series of mutations. But considering that a billion cells in our bodies
divide every day, something is bound to go wrong and mutations occur once in a while.
And they do, for an estimated 1.6 million people in the United States each year.

What do cancer stages and grades mean?

The stage of a cancer describes the size of a tumour and how far it has spread from
where it originated. The grade describes the appearance of the cancerous cells.

If you're diagnosed with cancer, you may have more tests to help determine how far it
has progressed. Staging and grading the cancer will allow the doctors to determine its
size, whether it has spread and the best treatment options.

Cancer stages

Different types of staging systems are used for different types of cancer. Below is an
example of one common method of staging:

• stage 0 – indicates that the cancer is where it started (in situ) and hasn't
spread
• stage I – the cancer is small and hasn't spread anywhere else
• stage II – the cancer has grown, but hasn't spread
• stage III – the cancer is larger and may have spread to the surrounding
tissues and/or the lymph nodes (part of the lymphatic system)
 • stage IV – the cancer has spread from where it started to at least one other
body organ; also known as "secondary" or "metastatic" cancer

Cancer grades

The grade of a cancer depends on what the cells look like under a microscope.

In general, a lower grade indicates a slower-growing cancer and a higher grade

indicates a faster-growing one. The grading system that's usually used is as follows:

• grade I – cancer cells that resemble normal cells and aren't growing rapidly
• grade II – cancer cells that don't look like normal cells and are growing faster
than normal cells
• grade III – cancer cells that look abnormal and may grow or spread more
aggressively