Transcript Growth Factors

Chapter 5
Neoplasia: A Disorder of Cell
Proliferation and Differentiation
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Neoplasia
• Neoplasms proliferate to form new tissue
• They do not wait for signals from the body that
the new tissue is needed
• They ignore signals to stop dividing
• They often do not mature normally (differentiate)
to do the “job” the tissue is supposed to do
• They do not die off (apoptosis) to keep the
number of total cells constant
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The Cell Cycle
• Normally, the
number of cells
produced = the
number of cells
that die
• The total
number of cells
in the body
S
remains
constant
Labile cell
M
G2
Permanent
cell
Mitosis
G1
Interphase
G0
Stable cell
R
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Growth Factors
• Cells divide
only when they
are told to do
so by growth
factors
• These cause
stable cells to
enter the cell
S
cycle and divide
Labile cell
M
G2
Permanent
cell
Mitosis
G1
Interphase
R
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G0
Stable cell
affected by
growth factors
Growth Factors
(cont.)
• Attach to receptor
proteins 
• Which often work by
affecting G proteins 
• Which turn on enzymes
(proteins) 
• Which make second
messengers 
• Which go down inside
the cell and make it
divide
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A Cell Creates Proteins Based on Its Genes
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Growth Factor
Receptors
• Now this cell is
ready to respond
to growth factors
from another cell
• They bind to the
receptors and
stimulate cell
division
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Proto-oncogenes
• The normal genes that code for normal proteins
used in cell division
– Growth factors
– Growth factor receptors
– G proteins
– Enzymes that produce second messengers
– Genes that turn the production of these
proteins on and off
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Oncogenes
• Oncogenes are mutated proto-oncogenes
• They still code for the proteins needed for cell division
• But they might produce
– Too much of the protein
– An abnormal protein
– Protein that turns on all by itself
– Protein that is made when it is not needed
– Protein that cannot turn cell division off
– Protein that should be made by a different cell
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Question
Tell whether the following statement is true or false.
Oncogenes code for normal proteins used in cell division.
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Answer
False
Rationale: The statement describes proto-oncogenes.
Oncogenes are mutated proto-oncogenes that code for
abnormal proteins.
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This Cell Has Been Infected With a
Cancer-causing Virus
• What has
changed?
• How could it
promote
uncontrolled cell
division?
• What oncogene
is to blame for
this?
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If You Want to Stop This Cell From
Dividing, What Should You Do?
• Give a drug that
stops other cells
from making the
growth factor?
• Give a drug that
blocks the growth
factor receptors?
• Give a drug that
inactivates growth
factors in the
extracellular fluid?
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Here’s Another Cell with the Same Cancer—
Would Any of These Treatments Work?
• A drug that stops
other cells from
making the growth
factor?
• A drug that blocks
the growth factor
receptors?
• A drug that
inactivates growth
factors in the
extracellular fluid?
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Checkpoints in Cell Division
Cyclins make sure
the cell has made
the proteins needed
G2
to separate the
chromosomes
M
Mitosis
G1
Cyclins check
that the DNA has S
been correctly
duplicated
Interphase
R
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Cyclin
proteins
Permanent
measure
cell
whether the
cell has
G0 large
grown
enough to
divide
Tumor Suppressor Proteins
• The checkpoints usually stop the division of mutated cells
• They keep most mutations from developing into cancer
• The proteins that control the checkpoints are called
tumor suppressor proteins
– Cyclins
– Cyclin-dependent kinases
– Cyclin inhibitors (p53)
• If the genes for these proteins were mutated, you might
get many more cancers
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Cell Division Requires Duplicating the DNA
• Telomeres: DNA sequences at the ends of the
chromosomes
– The enzymes that duplicate DNA attach here
– The end of the telomere does not get duplicated
– What will happen to the telomere as the cell
continues dividing?
• A man has a mutation that causes some of his cells
to rebuild their telomeres after every division. Is this
a good thing or a bad thing? Why?
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Oncogenesis
• Initiation: initial
mutation occurs
• Promotion: mutated
cells are stimulated
to divide
• Progression: tumor
cells compete with
one another and
develop more
mutations, which
makes them more
aggressive
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Labile cell
Normal Cells
• Normally, after
a cell has
divided, it
becomes either
a permanent
cell or a stable
cell
• These cells stop
reproducing
S
and continue
working for the
body
M
G2
Permanent
cell
Mitosis
Interphase
G1
G0
Stable cell
R
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Differentiation
• “Grown-up”
cells are
called
differentiated
because they
look different
from one
another
• You can tell a
spleen cell
from a skin
cell
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Cell Mutation
• When differentiated,
“working” cells mutate,
they form
differentiated
“working” tumors—
benign tumors
• When undifferentiated,
rapidly dividing cells
mutate, they form
rapidly dividing
tumors—malignant
tumors
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Question
When a well-differentiated cell mutates, is it more or less
likely to become a malignant tumor?
a. More
b. Less
c. Degree of differentiation has no bearing on whether a
tumor is malignant or benign.
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Answer
b. Less
The more differentiated a cell is when it mutates, the more
likely it is to become a benign tumor. If poorly
differentiated cells mutate, the tumor is more likely to
become malignant.
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Naming Tumors
• Benign tumors: tissue name + “-oma”
• Malignant tumors (cancers)
– Epithelial tissue: tissue name + “carcinoma”
– Mesenchymal tissue: tissue name + “sarcoma”
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Benign Tumors
• Contain cells that look like normal tissue cells
• May perform the normal function of the tissue (like
secreting hormones)
– This may lead to oversecretion
• Usually have a capsule around them
• Usually do not invade neighboring tissues
• But they can damage nearby organs by compressing
them
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Benign Uterine Tumor With Clearly
Defined Edges
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Malignant Tumors
• Contain cells that do not look like normal adult cells
• These cells divide rapidly, so:
– Tumors grow quickly
– Cells mutate faster and can change type
• The tumor does not have clear boundaries and sends
“legs” out into surrounding tissue (the word cancer
means “crab” and is based on these crablike legs)
• Do not perform the normal functions of the organ
– May secrete hormones associated with other
tissues
• Can compress and/or destroy the surrounding tissues
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Malignant Lung Tumor Invades
Surrounding Tissues
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Question
What gross anatomic feature of the lung tumor you just
saw makes it likely to be malignant?
a. The tumor is growing quickly.
b. The tumor has a poorly defined border.
c. Cells do not look like normal cells.
d. All of the above
e. b and c
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Answer
e. b and c
Rationale: Gross anatomy can be viewed with the naked
eye. Although rapid growth is a characteristic feature of
malignant tumors, this cannot be determined from the
slide. However, the lack of a clear border and the
different appearance of the group of cancer cells can be
clearly seen.
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Metastasis
• Cells in a primary
tumor develop the
ability to escape
and travel in the
blood
• Imagine you were
a cancer cell. What
abilities would you
need to survive in
the tumor?
• What abilities
would you need to
metastasize?
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Scenario
• Mrs. T has liver cancer
• Her doctor did an initial molecular diagnosis and
put her on targeted therapy; the tumor shrank by
almost 75%
• Two years later the tumor was growing again, and
this time it did not respond to the drug
• Last year she was diagnosed with metastases in
her femur that have not responded to the drug
either
• Mrs. T wants to know why the cancer cells stopped
responding. Are they not all the same cells?
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Manifestations of Cancer
• Changes in organ function (organ damage,
inflammation, and failure)
• Local effects of tumors (e.g., compression of
nerves or veins, gastrointestinal
obstruction)
• Ectopic hormones secreted by tumor cells
(paraneoplastic disorders)
• Nonspecific signs of tissue breakdown (e.g.,
protein wasting, bone breakdown)
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Changes in Organ Function
• Organ failure
• Benign tumors may cause overproduction of
normal organ secretions
• Malignant tumors may occasionally cause
overproduction (as in thyroid cancer), but
more commonly decrease production of
normal organ secretions
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Question
Why do malignant tumors usually cause a reduction in the
amount of hormones the affected organ produces?
a. Organ damage
b. Inflammation of the organ
c. Organ failure
d. All of the above
e. a and c
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Answer
d. All of the above
Rationale: Effects of malignant tumors on the organ
system include inflammation and damage, which
ultimately lead to organ failure. In all cases the organ
cannot function optimally, and is unable to secrete the
normal/typical amount of hormones.
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Local Effects of Tumor Growth
• Bleeding
• Compression of blood vessels
– Superior vena cava syndrome
– Portal hypertension
• Compression of lymph vessels
– Edema, ascites, effusion
• Compression of hollow organs
• Compression of nerves
– Pain, paralysis
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Paraneoplastic Syndromes
• Cancer cells produce hormones or hormone-like
proteins
– ADH
– ACTH
– PTH-related protein
• Cancer cells produce proteins that affect clotting
• Paraneoplastic neurologic disorders
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Generalized Effects of Cancer
• Cancer cachexia syndrome
– Weight loss
– Muscle wasting
– Weakness
– Anorexia
– Anemia
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