Cancer: How Cancer Cells Develop
Lecture Day 5
Cancer is Not a Single Disease
More than 100 diseases are classified under the term
cancer
Our bodies produce cancerous cells each day
But most are killed by our immune system
Cancer cells have unlimited potential to replicate (to
divide)
Normal cells are programmed to die: Damaged or replicate too
many times
Programmed cell death is called apoptosis
Cancer cells manage to avoid it and become “immortal”
© 2013 by John Wiley & Sons, Inc. All rights reserved.
Characteristics of Cancer Cells
Cancer can be defined as uncontrolled cell replication (cell
division)
normal mechanisms of cell regulation breakdown
Cancer cells disregard or don’t receive the chemical signals
that tell them it is time to stop dividing and die
Cancer cells lack differentiation
No specified function, make no contribution to the overall
functioning of a particular body part
Have no homeostatic function in the body
Have abnormal nuclei and chromosomes
© 2013 by John Wiley & Sons, Inc. All rights reserved.
The Cell Cycle
Regular pattern of growth for Eukaryotic Cells
Cells need nutrition, adequate size, and undamaged
DNA for successful division.
Has four main stages: Interphase [Gap 1,
Synthesis, Gap 2], Mitosis, cytokinesis
Governed by different chemical compounds
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Different Cells, Different Rates
Different Cells divide at different rates based on
the needs of the organism
G1 Stage also is dependent on cell type
Cells in embryos and children are shorter than
adults
Intestinal lining cells divide quicker
Some cells divide rarely and stay in the G0 Stage
The Cell Cycle
Critical Check Point 3:
2 copies of DNA properly
Attached to cytoskeleton
Critical Check Point 2:
DNA and centrosomes
copied correctly
Critical Check Point 1:
DNA checked for damage
Right conditions for division
checked
Proto-Oncogenes and Tumor-Suppressor
Genes
Tumor-suppressor genes are growth-stoppers
Tumor-suppressor genes can mutate
When altered no longer regulate the cell cycle and will not promote apoptosis
Such mutations are referred to as “loss-of function” mutations
Proto-oncogenes are growth promoters
When proto-oncogenes mutate, they form oncogenes - genes that cause cancer
Because there are many proto-oncogenes in each cell, it is possible to form
many oncogenes in one cell
Oncogenes disrupt cellular function, so the more oncogenes that are activated,
the worse off that cell will be
© 2013 by John Wiley & Sons, Inc. All rights reserved.
Proto-Oncogenes
© 2013 by John Wiley & Sons, Inc. All rights reserved.
Tumor-Suppressor Gene – “TP53”
The tumor-suppressor gene, TP53, gives directions for the
making of protein p53
p53 works as a general manager of cell functioning
It halts cell division in an abnormal cell
Unless - and until - the damaged DNA is repaired
If the damaged DNA cannot be repaired
The TP53 gene and its protein, p53, initiate a series of
physiological changes that ultimately lead to the cell’s death
Cancer cells may have faulty TP53 genes
© 2013 by John Wiley & Sons, Inc. All rights reserved.
TP53 Tumor-Suppressor Gene
© 2013 by John Wiley & Sons, Inc. All rights reserved.
Telomeres and Telomerase
Telomeres are short pieces of DNA located at the tips of chromosomes
They are maintained by an enzyme called telomerase
Each time a cell replicates, a little bit of the telomere is snipped off
Stops making telomerase soon after birth and telomere length gradually
decreases
A typical cell replicates 50 or 60 times before the entire telomere is gone
At that point the cell stops replicating, and eventually it wears out and dies
If telomerase is present in the cell
The telomere will be repaired after every cycle of cell division, and the cell will
continue to divide indefinitely
A cell that develops the ability to maintain telomerase in its cytoplasm lives
“forever,” and is on its way to being a cancerous cell
© 2013 by John Wiley & Sons, Inc. All rights reserved.
The Immune System and Cancer
The immune system destroys most
potentially cancerous cells
It recognizes these cells as “other” or
“nonself”
Looks for non-self proteins on cell
surfaces
Reacts as it would to any other foreign
tissue
Many cancer cells have antigens on their
surfaces that are not found on normal cells
of the body
cytotoxic T cells and natural killer cells
recognize the abnormal antigens on the
potentially cancerous cells
And destroy them
© 2013 by John Wiley & Sons, Inc. All rights reserved.
The Immune System and Cancer
Cancer cells have mechanisms that allow them
to avoid destruction by the immune system
Some include mechanisms that actively seek to
avoid the body’s defenses
Other cancers simply overwhelm the immune
system defenses by multiplying more rapidly
than they can be killed off
If the immune system is weakened
Cancerous cells have a distinct advantage
© 2013 by John Wiley & Sons, Inc. All rights reserved.
Cancer Progression – “Carcinogenesis”
Once they have overcome the body’s defenses,
cancer cells can continue to grow and multiply
unchecked
Passing their mutations to the next generation
of cells
Carcinogenesis has begun
The mutated cells may successfully outcompete
normal cells for space and nourishment
© 2013 by John Wiley & Sons, Inc. All rights reserved.
Cancer Progression –
“Angiogenesis”
When a malignant cancerous growth reaches about 1 million cells
(approximately 1 or 2 millimeters in diameter)
The cells in the interior can no longer receive enough nutrients, and
they begin depositing their waste products within the cell cluster
This ball of cells is called a carcinoma in situ (“cancer in place”) and it now
needs its own blood supply if it is to survive
It starts to produce its own growth-enhancing proteins
And, secretes angiogenic compounds to lure blood vessels into the
tumor
Angiogenesis is the process by which new blood vessels are formed to
feed a tumor
Once the tumor has a blood supply, it becomes immortal
The tumor will grow and spread until it kills its host
Unless it is cut out, killed with chemicals, damaged by radiation or another substance,
or starved of its nutrient supply
© 2013 by John Wiley & Sons, Inc. All rights reserved.
Carcinogenesis
© 2013 by John Wiley & Sons, Inc. All rights reserved.
Cancer Progression
Cancers can invade almost any body tissue
From skin and bone, to organs like the lungs, liver, and
intestine
Once a tumor has become firmly established
Cancerous cells often break away from the original mass
and travel through the bloodstream or lymph
Metastasis is the process by which the original cancerous
tumor spreads throughout the body
Traveling cells are deposited at “secondary sites,” where
other tumors may develop
Metastatic tumors at secondary sites may continue to
grow even if the primary tumor is killed or removed
© 2013 by John Wiley & Sons, Inc. All rights reserved.
