Normal vs Cancer Cell

• 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. 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.

• 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.
 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 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.
 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 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.
Biochemical Explanation
Evading Growth (Tumour) 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.
• Second 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 vs Immortality
• Normal cells are mortal, that is, they have a lifespan. Cells
aren’t designed to live foreverand 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 cell 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.
 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.
How to plan clinical cancer
Genetic mutation
research
RNA expression Protein expression
Isolate genomic Isolate total RNA Isolate total
DNA from healthy from healthy and proteins from
and diseased tissue diseased tissue healthy and
sample such as sample such as diseased tissue
breast tissues or breast tissues sample such as
from blood breast tissues

Design gene specific Design gene specific Quantify and

primers primers Perform SDS PAGE
Perform PCR Perform real time Perform Western
PCR blotting or IHC with
specific antibodies
Send for Quantify by Analyse the
Sequencing comparison how expression of
much increase or proteins whether
decrease in high or low in
expression comparison