Cancer Cells vs Normal Cells

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Cancer Cells vs. Normal Cells:
How Are They Different?
By Lynne Eldridge, MD | Reviewed by Grant Hughes, MD
Updated September 07, 2018
There are many differences between cancer cells and normal cells. Some of the
differences are well known, whereas others have only been recently discovered and are
less well understood. You may be interested in how cancer cells are different as you are
coping with your own cancer or that of a loved one. For researchers, understanding how
cancer cells function differently from normal cells lays the foundation for developing
treatments designed to rid the body of cancer cells without damaging normal cells.
The first portion of this list discusses the basic differences between cancer cells and
healthy cells. For those who are interested in some of the more difficult-to-understand
differences, the second portion of this list is more technical.
A brief explanation of the proteins in the body that regulate cell growth is also helpful in
understanding cancer cells. Our DNA carries genes that in turn are the blueprint for
proteins produced in the body. Some of these proteins are growth factors, chemicals that
tell cells to divide and grow. Other proteins work to suppress growth. Mutations in
particular genes (for example, those caused by tobacco smoke, radiation, ultraviolet
radiation, and other carcinogens) can result in the abnormal production of proteins. Too
many may be produced, or not enough, or it could be that the proteins are abnormal and
function differently.
Cancer is a complex disease, and it is usually a combination of these abnormalities that
lead to a cancerous cell, rather than a single mutation or protein abnormality.
Cancer Cells vs. Normal Cells
Below are some of the major differences between normal cells and cancer cells, which in
turn account for how malignant tumors grow and respond differently to their
surroundings than benign tumors.

Growth—Normal cells stop growing (reproducing) when
enough cells are present. For example, if cells are being
produced to repair a cut in the skin, new cells are no longer
produced when there are enough cells present to fill the hole;
when the repair work is done. In contrast, cancer cells don’t
stop growing when there are enough cells present. This
continued growth often results in a tumor (a cluster of cancer
cells) being formed. Each gene in the body carries a blueprint
that codes for a different protein. Some of these proteins are
growth factors, chemicals that tell cells to grow and divide. If
the gene that codes for one of these proteins is stuck in the “on”
position by a mutation (an oncogene)—the growth factor
proteins continue to be produced. In response, the cells continue
to grow.

Communication—Cancer cells don’t interact with other cells
as normal cells do. Normal cells respond to signals sent from
other nearby cells that say, essentially, “you’ve reached your
boundary.” When normal cells “hear” these signals they stop
growing. Cancer cells do not respond to these signals.

Cell repair and cell death—Normal cells are either repaired or
die (undergo apoptosis) when they are damaged or get old.
Cancer cells are either not repaired or do not undergo apoptosis.
For example, one protein called p53 has the job of checking to
see if a cell is too damaged to repair and if so, advise the cell to
kill itself. If this protein p53 is abnormal or inactive (for
example, from a mutation in the p53 gene,) then old or
damaged cells are allowed to reproduce. The p53 gene is one
type of tumor suppressor gene that code for proteins that
suppress the growth of cells.

Stickiness—Normal cells secrete substances that make them
stick together in a group. Cancer cells fail to make these
substances, and can “float away” to locations nearby, or
through the bloodstream or system of lymph channels to distant
regions in the body.

Ability to Metastasize (Spread)—Normal cells stay in the area
of the body where they belong. For example, lung cells remain
in the lungs. Cancer cells, because they lack the adhesion
molecules that cause stickiness, are able to travel via the
bloodstream and lymphatic system to other regions of the
body—they have the ability to metastasize. Once they arrive in
a new region (such as lymph nodes, the lungs, the liver, or the
bones) they begin to grow, often forming tumors far removed
from the original tumor. (Learn more about how cancer
spreads.)

Appearance—Under a microscope, normal cells and cancer
cells may look quite different. In contrast to normal cells,
cancer cells often exhibit much more variability in cell size—
some are larger than normal and some are smaller than normal.
In addition, cancer cells often have an abnormal shape, both of
the cell, and of the nucleus (the “brain” of the cell.) The nucleus
appears both larger and darker than normal cells. The reason for
the darkness is that the nucleus of cancer cells contains excess
DNA. Up close, cancer cells often have an abnormal number of

chromosomes that are arranged in a disorganized fashion.
The rate of growth—Normal cells reproduce themselves and
then stop when enough cells are present. Cancer cells reproduce
rapidly before the cells have had a chance to mature.

Maturation—Normal cells mature. Cancer cells, because they
grow rapidly and divide before cells are fully mature, remain
immature. Doctors use the term undifferentiated to describe
immature cells (in contrast to differentiated to describe more
mature cells.) Another way to explain this is to view cancer
cells as cells that don’t “grow up” and specialize into adult
cells. The degree of maturation of cells corresponds to
the "grade" of cancer. Cancers are graded on a scale from 1 to
3 with 3 being the most aggressive.

Evading the immune system—When normal cells become
damaged, the immune system (via cells called lymphocytes)
identifies and removes them. Cancer cells are able to evade
(trick) the immune system long enough to grow into a tumor by
either by escaping detection or by secreting chemicals that
inactivate immune cells that come to the scene. Some of the
newer immunotherapy medications address this aspect of
cancer cells.

Functioning—Normal cells perform the function they are
meant to perform, whereas cancer cells may not be functional.
For example, normal white blood cells help fight off infections.
In leukemia, the number of white blood cells may be very high,
but since the cancerous white blood cells are not functioning as
they should, people can be more at risk for infection even with
an elevated white blood cell count. The same can be true of
substances produced. For example, normal thyroid cells
produce thyroid hormone. Cancerous thyroid cells (thyroid
cancer) may not produce thyroid hormone. In this case, the
body may lack enough thyroid hormone (hypothyroidism)
despite an increased amount of thyroid tissue.

Blood supply—Angiogenesis is the process by which cells
attract blood vessels to grow and feed the tissue. Normal cells
undergo a process called angiogenesis only as part of normal
growth and development and when new tissue is needed to
repair damaged tissue. Cancer cells undergo angiogenesis even
when growth is not necessary. One type of cancer treatment
involves the use of angiogenesis inhibitors—medications that
block angiogenesis in the body in an effort to keep tumors from
growing.
More Differences Between Cancer Cells and Normal Cells
This list contains further differences between healthy cells and cancer cells. For those
who wish to skip these technical points, please skip to the next subheading labeled
summarizing the differences.

Evading growth suppressors—Normal cells are controlled by
growth (tumor) suppressors. There are three main types of
tumor suppressor genes that code for proteins that suppress
growth. One type tells cells to slow down and stop dividing.
One type is responsible for fixing changes in damaged cells.
The third type is in charge of the apoptosis noted above.
Mutations that result in any of these tumor suppressor genes
being inactivated allow cancer cells to grow unchecked.

Invasiveness—Normal cells listen to signals from neighboring
cells and stop growing when they encroach on nearby tissues
(something called contact inhibition.) Cancer cells ignore these
cells and invade nearby tissues. Benign (non-cancerous) tumors
have a fibrous capsule. They may push up against nearby
tissues but they do not invade/intermingle with other tissues.
Cancer cells, in contrast, don’t respect boundaries and invade
tissues. This results in the fingerlike projections that are often
noted on radiologic scans of cancerous tumors. The word
cancer, in fact, comes from the latin word for crab used to
describe the crablike invasion of cancers into nearby tissues.

Energy Source—Normal cells get most of their energy (in the
form of a molecule called ATP) through a process called the
Krebs cycle, and only a small amount of their energy through a
different process called glycolysis. Whereas normal cells
produce most of their energy in the presence of oxygen, cancer
cells produce most of their energy in the absence of oxygen.
This is the reasoning behind hyperbaric oxygen treatments that
have been used experimentally (with disappointing results thus
far) in some people with cancer.

Mortality/Immortality—Normal cells are mortal, that is, they
have a lifespan. Cells aren’t designed to live forever, and just
like the humans they are present in, cells grow old. Researchers
are beginning to look at something called telomeres, structures
that hold DNA together at the end of the chromosomes, for their
role in cancer. One of the limitations to growth in normal cells
is the length of the telomeres. Every time a cell divides, the
telomeres get shorter. When the telomeres become too short, a
cell can no longer divide and the cell dies. Cancer cells have
figured out a way to renew telomeres so that they can continue
to divide. An enzyme called telomerase works to lengthen the
telomeres so that the cell can divide indefinitely—essentially
becoming immortal.

Ability to "hide"—Many people wonder why cancer can recur
years, and sometimes decades after it appears to be gone
(especially with tumors such as estrogen receptor positive
breast cancers.) There are several theories why cancers may
recur. In general, it's thought that there is a hierarchy of cancer
cells, with some cells (cancer stem cells) having the ability to
resist treatment and lie dormant. This is an active area of
research, and extremely important.

Genomic instability—Normal cells have normal DNA and a
normal number of chromosomes. Cancer cells often have an
abnormal number of chromosomes and the DNA becomes
increasingly abnormal as it develops a multitude of mutations.
Some of these are driver mutations, meaning they drive the
transformation of the cell to be cancerous. Many of the
mutations are passenger mutations, meaning they don’t have a
direct function for the cancer cell. For some cancers,
determining which driver mutations are present (molecular
profiling or gene testing) allows physicians to use targeted
medications which specifically target the growth of the
cancer. The development of targeted therapies such as EGFR
inhibitors for cancers with EGFR mutations is one of the more
rapidly growing and progressing areas of cancer treatment.
The Multiple Changes Needed for a Cell to Become Cancerous
As noted above, there are many differences between normal cells and cancer cells. Also
noteworthy is the number of “checkpoints” that need to be bypassed for a cell to become
cancerous.

The cell needs to have growth factors that prompt it to grow

even when growth is not necessary.
The has to evade proteins that direct cells to stop growing and

die when they become abnormal.
The cell needs to evade signals from other cells,

The cells need to lose the normal “stickiness” (adhesion
molecules) that normal cells produce.
All in all, it is very difficult for a normal cell to become cancerous, which may seem
surprising considering that one in two men and one in three women will develop cancer
in their lifetime. The explanation is that in the normal body, roughly three billion cells
divide every single day. “Accidents” in the reproduction of the cells caused by heredity
or carcinogens in the environment during any of those divisions can create a cell that,
following further mutations, can develop into a cancer cell.
Benign vs. Malignant Tumors
As noted above, there are many differences in cancer cells and normal cells which make
up either benign or malignant tumors. In addition, there are ways that tumors containing
cancer cells or normal cells behave in the body.
Differences Between a Malignant and Benign Tumor
The Concept of Cancer Stem Cells
After discussing these many differences between cancer cells and normal cells, you may
be wondering if there are differences between cancer cells themselves. That there may be
a hierarchy of cancer cells—some having different functions than others—is the basis of
discussions looking at cancer stem cells as discussed above.
We still don't understand how cancer cells can seemingly hide for years or decades and
then reappear. It's thought by some that the "generals" in the hierarchy of cancer cells
referred to as cancer stem cells may be more resistant to treatments and have the ability to
lie dormant when other soldier cancer cells are eliminated by treatments such as
chemotherapy. While we currently treat all the cancer cells in a tumor as being identical,
it's likely that in the future treatments will take into further consideration some of the
differences in cancer cells in an individual tumor.
Bottom Line on Differences Between Normal Cells and Cancer Cells
Many people become frustrated, wondering why we haven't yet found a way to stop all
cancers in their tracks. Understanding the many changes a cell undergoes in the process
of becoming a cancer cell can help explain some of the complexity. There is not one step,
but rather many, that are currently being addressed in different ways. In addition to this,
it's important to realize that cancer isn't a single disease, but rather hundreds of different
diseases. And even two cancers that are the same with regard to type and stage, can
behave very differently. If there were 200 people with the same type and stage of cancer
in a room, they would have 200 different cancers from a molecular standpoint.
It is helpful, however, to know that as we learn more about what makes a cancer cell a
cancer cell, we gain more insight into how to stop that cell from reproducing, and perhaps
even making the transition to becoming a cancer cell in the first place. Progress is already
being made in that arena, as targeted therapies are being developed which discriminate
between cancer cells and normal cells in their mechanism. And research on
immunotherapy is just as exciting, as we are finding ways to "stimulate" our own
immune systems to do what they already know how to do. Find cancer cells and eliminate
them. Figuring out the ways in which cancer cells "disguise" themselves and hide has
resulted in better treatments, and uncommonly, complete remissions, for some people
with the most advanced solid tumors.
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