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CELL GROWTH
ABNORMALITIES
HA MWAKYOMA, MD
Basics of signal transduction
• Cell communication, or signal
transduction, is simply the means by which
cells in the body respond to signals
coming from outside those cells.
• The purpose of this chemical
communication is to coordinate functions
inside the cell, between cells or between
organs in the body, allowing us the means
to respond to our external environment
NORMAL SITUATION:
• Normally, cell division is a very carefully
regulated process that ensures the body has
neither too few nor too many of a given cell type.
• Some cell types in the body wear out quickly
and need to be continuously replaced as they
die, such as most blood cells and cells lining the
digestive tract.
• The production of these cells must be
precisely regulated based on their rate of cell
death so that the body has the exact number of
cells it needs.
CELL DIVISION:
Relationship with cancer
• Abnormal - or more specifically uncontrolled, rapid cell growth is a
central feature of cancer.
• Virtually every cancer is caused by
mutations of DNA, the genetic material
that controls how cells behave.
• Genes that regulate cell division are
most susceptible to mutations, which
may lead to abnormal cell growth
The Cell Cycle
• In order to proliferate, both normal and
cancerous cells must undergo the process
of cell division. This process is the end
result of the cell cycle. The cell cycle has
two major phases:
• Mitosis
• Interphase
THE CELL CYCLE cont-• Mitosis is the process by which a parent
cell produces a pair of genetically
identical daughter cells. It is part of the
normal cell cycle. The cell cycle is divided
into two distinct periods:
• Interphase (cell growth)
• Mitotic phase (cell division)
THE CELL CYCLE cont-• Interphase is the period of a cell’s life
when it carries out its normal growth
and metabolic activities. It is also
the time during which a cell
undergoes a closely ordered
sequence of activities in preparation
for cell division.
.
THE CELL CYCLE cont-• Interphase is made up of three subphases. During the G1 phase, the cell
produces the proteins needed to copy
the cellular DNA, which occurs during the
second S phase of the cell cycle. (There
must be two identical copies of the DNA so
that one copy is passed to each of the
daughter cells).
Interphase cont-• During the final G2 phase, which lies
between the replication of the DNA and
the beginning of mitosis (when the cell
actually divides), the cell produces
proteins needed for cell division.
BALANCE OF NORMAL CELL
DIVISION:
• This balance may be upset by either the
abnormal over activation of oncogenes or the
abnormal inactivation of tumor suppressor
genes.
• These genetic events may be caused by
environmental toxins, random internal changes,
and
• also may be inherited from a family who has a
history of cancer where a defective growthregulatory gene is passed down through
generations.
CELL BALANCE cont-• Cell division can get out of control when
damage to specific genes in the cell’s DNA
results in abnormally functioning growth
regulatory proteins.
• For instance, melanoma is a cancer that arises
in the melanocytes, the cells that produce
melanin. The primary cause of melanoma is
damage to the DNA of melanocytes by UV
radiation from the sun.
• When we are overexposed to the sun and
receive too much UV radiation, the DNA may be
damaged, thus resulting in abnormal cell growth
and eventually, cancer.
CANCER:
• Cancer is a disease of the genes
• it arises from defects in certain genes,
• the genes that normally regulate cell growth and cell
death.
• Some genes, known as oncogenes, promote normal
cell growth.
• Other genes, known as tumor suppressor genes, have
the opposite effect, to retard cell growth.
• The normal division of our cells is a delicate balance of
positive and negative growth signals from these
genes
CANCEROUS CELLS:
• When a cell becomes cancerous, over
time a tumor forms from these abnormal
cells.
• Because the tumor is made up of
defective cells, it cannot function as it
should. The body suffers in two ways:
- from both the loss of the normal
function of that tissue and
- from the damage to other tissues
Abnormal cell growth
• The signals that control cell growth are proteins.
• Cells use your genes to make these proteins.
• Each gene is the instruction for a particular protein.
• Occasionally a gene is damaged,
- resulting in a change, or gene mutation which may
sometimes affect a protein so that it no longer works
properly.
• Mutations in certain crucial genes can cause abnormal
cell growth, and eventually turn a healthy cell into a
cancer cell
Steps towards malignancy:
• A healthy cell does not turn into a cancer cell
overnight.
• Its behaviour gradually changes, a result of damage
to between three and seven of the hundreds of genes
that control cell growth, division and life span.
• First, the cell starts to grow and multiply.
• Over time, more changes may take place.
• The cell and its descendants may eventually become;
 immortal,
 escape destruction by the body's defences,
 develop their own blood supply and
 invade the rest of body.
Uncontrolled growth
• A cell is continuously receiving
messages, both from its own genes and
from other cells.
Some tell it to grow and multiply,
others tell it to stop growing and rest, or
even to die.
• If there are enough 'grow' messages, the
next stage of the cell's life starts.
Uncontrolled growth cont-• In a cancer cell;
 the messages to grow may be altered, or
 the messages to stop growing or to die may
be missing.
• The cell then begins to grow uncontrollably
and divide too often.
• Some messages tell the cell to grow and
multiply ('accelerators'),
• others tell it to stop growing and rest
('brakes').
UNCONTROLLED CELL
GROWTH
Living forever
• Every time a normal cell divides, the ends of its
chromosomes become shorter.
• Once they have worn down, the cell dies and is
replaced.
• Cancer cells cheat this system - they retain their long
chromosomes by continually adding bits back on.
• This process allows cancer cells to become immortal.
--Cells from Henrietta Lacks, an American woman who
was diagnosed with cervical cancer in 1951, are still
growing. They are used in research laboratories all over
the world, many years following her death.
BREAST CANCER CELLS
DIVIDING
Invading the body
• Most normal cells in your tissues stay
put, stuck to each other and their
surroundings.
• Unless they are attached to something,
they cannot grow and multiply.
• If they become detached from their
neighbours, they commit suicide, by a
process known as apoptosis.
Invading the body cont-• But in cancer cells the normal selfdestruct instructions do not work, and
they can grow and multiply without being
attached to anything.
• This allows them to invade the rest of the
body, travelling via the bloodstream to
start more tumours elsewhere
(metastasis)
METASTASIS IN BLOOD STREAM
Genetic chaos
• Every time a healthy human cell
divides, it copies all its genes, which
are bundled up into 46 chromosomes.
This process has several
checkpoints to ensure that each new
cell gets a near-perfect copy.
Genetic chaos cont-• But in a cancer cell, these checkpoints
are often missing. The result is chaos:
parts of chromosomes may be lost,
rearranged or copied many times and
the genes are more likely to acquire
further mutations. Some of these may
allow the cell to escape other checking
and repair mechanisms
Chromosomes from normal cell
(above) and from cancer cell below
Repair or die
• In normal cells, gene damage is
usually quickly repaired. If the
damage is too severe, the cell is
forced to die. An important protein
called p53 checks for gene damage
in normal cells, and kills them if the
damage is too great to repair.
Repair or die cont-• However, in cancer cells these
checking mechanisms are
defective. Cancer cells often have an
altered p53 protein, which does not
work properly, allowing cancer cells
to survive, despite their dangerously
garbled genetic material
Photomicrograph of a cancer cell
Escaping destruction
• When you are healthy, every part of your
body has just the right number of cells:
• the birth and death of each one is
carefully controlled.
• Any cells that start to multiply too much or
in the wrong place are either stopped from
growing, or forced into suicide by the
process of apoptosis.
Escaping destruction cont-• In cancer cells, these instructions are
either missing, altered or ignored. So
cancer cells escape destruction, and
continue to multiply in an uncontrolled
way.
• Cell death is controlled in the process of
apoptosis
What causes gene mutations?
• Chemicals viruses and radiation can damage
genes.
• However, most mutations occur when the cell
makes errors as it copies its genes.
• Genes are made out of DNA, a chemical code
with four different 'letters'.
• Each time one of your cells divides, it must copy
around 6000 million letters of DNA code.
• Occasionally, mistakes are made, causing
mutations.
• Most of these are corrected immediately, but a
few manage to escape unnoticed
Normal Differentiation
• Cellular differentiation is the process by
which a cell changes its structure so that it
can perform a specific function. Cells can
range from poorly differentiated to welldifferentiated. The most poorly
differentiated cells (generally called stem
cells) are capable of acquiring a range of
new functions
Cell differentiation
• Stem cells are important to your overall
health. For example, after severe trauma,
they provide a pool of cells that can
differentiate into specific cell types and
repair tissue
Cell differentiation cont-• Well-differentiated cells are mature, fully
developed cells that are ready to carry out
their particular function. A good example of
cell differentiation is blood cells
Cell differentiation cont-• There are three major types of blood cells:
red blood cells, white blood cells, and
platelets. Each has specific
characteristics, functions, and life spans,
yet all have differentiated from stem cells.
Image below illustrates the process of
cellular differentiation. See the Focus Box
below to learn more about the relationship
between cell differentiation and cancer
CELL DIFFERENTIATION
Cell differentiation and cancer
• Cell differentiation is important to the study
of cancer because a cell’s degree of
differentiation is associated with its ability
to proliferate.
• Poorly differentiated cells are highly
proliferative,
• moderately differentiated cells are
moderately proliferative, and
Cell differentiation and cancer cont• well-differentiated cells are either unable
to proliferate or
- proliferate at a very slow rate.
• Aggressive cancers are often
characterized by poorly differentiated
cells, while less aggressive cancers
tend to contain moderately or welldifferentiated cells
Control of rate of cell proliferation
• In healthy tissues, the processes of
mitosis and differentiation are tightly
regulated. This is how the body ensures
that only the correct number of cells is
produced. The body has two methods for
controlling the rate of cell proliferation:
• Growth factors
• Contact inhibition
Control of rate of cell proliferation
• Growth factors stimulate mitosis and/or
cellular differentiation.
• If a cell needs to be replaced (due to damage,
natural apoptosis, or some other reason), it will
secrete growth factors that stimulate the cell to
either undergo mitosis or differentiate.
• Contact inhibition stops cells from
proliferating. Normally, individual cells maintain
a small amount of “personal space”.
• Under normal conditions, cells that become
crowded and begin to touch each other will
simply stop growing
Control of rate cell proliferation
cont-• Exactly how contact inhibition works
is still unknown, however scientists
believe that contact between cells
triggers the release of growth
inhibitory factors. Unlike growth
factors, growth inhibitory factors tell
cells to stop dividing.
Normal cell growth.
• In the case of normal cell proliferation,when the
appropriate number of cells has been produced
(and cells begin to crowd each other) growth
inhibitory factors trigger a negative feedback
mechanism to reduce the rate of cell growth.
• While positive feedback can occur normally, the
production of excess growth factors by cells
drives an abnormal positive feedback loop.
Abnormal Cell Growth
• In order for the tissues of the body to
maintain such precise control over the
growth of its cells, it has developed a
system of feedback loops that detect and
compensate for deviations from the
normal. For every situation controlled by a
feedback loop, the body has a set point it
recognizes as normal.
Abnormal cell growth cont-• Not all abnormally growing cells are
cancerous. For example, the term
hyperplasia refers to a type of
noncancerous growth consisting of rapidly
dividing cells, which leads to a larger than
usual number of structurally normal cells.
Hyperplasia may be a normal tissue
response to an irritating stimulus.
Abnormal cell growth cont-• Although hyperplasia is considered
reversible, it some cases it indicates an
increased risk of cancer. An example is
hyperplasia of the lining of the uterus
(endometrium).
• Dysplasia is another noncancerous type of
abnormal cell growth characterized by the
loss of normal tissue arrangement and cell
structure.
Dysplasia cont-• Dysplastic cells lose the normal
architecture that characterizes normal
tissues, and may show physical and
chemical changes that distinguish them
from their normal counterparts
• They may have changes in their DNA, or
they may have visible changes in their cell
structures (*especially the cell nucleus)
that can be seen under the microscope.
Dysplasia cont-• These visible changes are often useful in
detecting dysplasia early, before it
progresses, as it sometimes (but not
always) does lead to cancer. An example
is cervical dysplasia, which may become
cervical cancer if left untreated over a
long period of time.
Dysplasia cont-• The most severe form of dysplasia,
carcinoma in situ, can actually be
considered a form of cancer.
• In Latin, the term "in situ" means "in
place," so carcinoma in situ refers to an
uncontrolled growth of cells that remains in
the original location (in place) and does
not invade surrounding tissue as cancer
cells eventually do
Carcinoma in situ:
• Carcinoma in situ, however, is
considered more serious than
moderate dysplasia because the risk
of local invasion is much higher. This
is why, when discovered, carcinoma
in situ is usually removed surgically.
The following Image illustrates the
different types of abnormal cell
growth.
Types of abnormal cell growth