Download Features of Cancer Cells

Radiobiology
Lec 2:
stage 2:
2.Carcinogenesis and the Cell Cycle
2.1.Oncogenes:
Genes that are mutated or synthesized in abnormally excessive amounts
and easily transform normal cells into cancer cells are termed
oncogenes.
The development of cancer at the cellular level is termed carcinogenesis.
The combination of mutations that affect biological events such as cell
survival,
growth
control
and
differentiation
is
the
basis
for
carcinogenesis.
What is the cancer?
Cancer is a disorder characterized by the continuous proliferation of cells.
This event happens when the increase in the number of excessively
proliferating cells is not balanced by normal cell loss.
These cells continuously invade and damage the organs of organisms.
This imbalance arises from both the genetic abnormalities of cancer cells
and the inability of the organism to recognize and destroy these cells.
Features of Cancer Cells:
Tumor cells gain several phenotypic features during the development of
cancer. Those changes cause the rapid and uncontrolled proliferation of
tumor cells, as well as their spread to surrounding tissues. In addition,
those cell scan survive independently in specific microenvironments and
have the ability to metastasize.
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Unique Features of Cancer Cells:
1. Clonal origin:
Most cancer cells originate from just one abnormal cell. However, some
cancers arise from more than one malign clone. These clones are formed
because of either field damage (tissue cells exposed to more than one
carcinogen) or heritable defects in some genes.
2. Immortality:
Most normal cells can undergo a limited number of divisions. On the
other hand, cancer cells can undergo an unlimited number of divisions
and form endless numbers of cells. One of the mechanisms for
immortality is associated with telomeres, which are the tips of
chromosomes.
Telomeres cap and protect the terminal ends of chromosomes. The name
telomere literally means, “end part.” Mammalian telomeres consist of
long arrays of TTAGGG repeats that range in total length anywhere from
1.5 to 150 kilobases. Each time a normal somatic cell divides; telomeric
DNA is lost from the lagging strand because DNA polymerase cannot
synthesize new DNA in the absence of an RNA primer. Successive
divisions lead to progressive shortening, and after 40 to 60 divisions, the
telomeres in human cells are shortened dramatically, so that vital DNA
sequences begin to be lost. At this point, the cell cannot divide further
and undergoes senescence. Telomere length has been described as the
“molecular clock” or generational clock because it shortens with age in
somatic tissue cells during adult life. Stem cells in self- renewing tissues
and cancer cells in particular, avoid this problem of aging by activating
the enzyme telomerase. Telomerase is a reverse transcriptase that
includes the complementary sequence to the TTAGGG repeats and so
continually rebuilds the chromosome ends to offset the degradation that
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occurs with each division. Virtually all human tumor cell lines and
approximately 90% of human cancer biopsy specimens exhibit
telomerase activity.
By contrast, normal human somatic tissues, other than stem cells, do not
possess detectable levels of this enzyme. It is an attractive hypothesis that
both immortalization and carcinogenesis are associated with telomerase
expression.
During normal cell differentiation in, these telomeres shorten. However,
the telomeres are renewed by the effect of the enzyme telomerase in
cancer cells and stem cells. Telomerase activity normally decreases
during cell differentiation. Since the cell loses its capacity for
proliferation, fully differentiated cells enter a resting state and
consequently die. However, telomerase retains its efficacy in several
cancer types, or it is reactivated. Therefore, the telomere length remains
constant in these cells and they proliferate indefinitely (they become
immortal).
3. Genetic instability:
This situation is caused by defects in the DNA repair process and in
DNA mismatch recognition, which results in the heterogeneity of cancer
cells. Cancer cells form clones that gradually respond less and less to the
proliferation control mechanism. The ability of these clones to survive in
foreign environments also gradually increases and they gain the ability to
metastasize.
4. Loss of contact inhibition:
Normal cells growing in culture medium cannot divide if they do not
stick to the bottom layer. Normal cells also lose their ability to divide
when they form a layer across the whole surface. They do not divide,
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even in the presence of all of the required growth factors and other
nutritional elements in the Petri dish. Cancer cells, however, divide
independently without needing to stick to the bottom layer of the Petri
dish. Furthermore, they continue to grow even when they have formed
more than one layer in the cell culture.
5. Continuous increase in proliferation:
This situation is a characteristic of cancer cells in culture medium.
Although cancer cells consume the required nutrition factors, they
continue to grow, and they actually end up killing themselves.
6. Metastasis:
This feature is not found in benign tumors and normal cells. Metastasis
occurs because of the loss of cellular proteins responsible for adherence
to the extracellular matrix, intercellular interaction defects, abnormalities
in cell adherence to the basal membrane, abnormalities in basal
membrane production, or the destruction of basal membrane by enzymes
like metalloproteases.
2.2.Cell cycle checkpoints:
Normal cells have mechanisms for detecting errors in the DNA sequence.
A group of repair mechanisms replace damaged nucleotides with normal
molecules when the DNA is damaged. These mechanisms ensure that the
genetic material in each of the two daughter cells is the same as that of
the mother cell.
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A checkpoint is one of several points in the eukaryotic cell cycle at which
the progression of a cell to the next stage in the cycle can be halted until
conditions are favorable (figure 2.1).
-First checkpoint of the cell cycle:
This is located in the late G1 phase just prior to the S phase. DNA should
be error-free before it exits from G1, and even extracellular signals
specific for DNA synthesis and all of the mechanisms should work
properly.
If any damage is detected, the cell will not be allowed to continue to the S
phase of interphase, and try to either repair the damage or die by
apoptosis.
-Second checkpoint of the cell cycle:
This
is
located
in
the late
G2phase
just
prior
to
the
M
phase.G2checkpoint ensures all of the chromosomes have been replicated
and that the replicated DNA is not damaged before cell enters
mitosis.Cell cycle inhibitors stop the cell cycle until they are sure that the
new daughter cells will have perfect genetic copies of the DNA in the
original cell. If DNA replication does not finish entirely and correctly, or
not all of the proteins, spindle cells and other materials needed for mitosis
are formed completely, the cell cycle stops at this checkpoint until all
errors have been corrected. It then enters the M phase.
- Third checkpoint of the cell cycle:
This is located in the late M phase. M checkpoint determines whether all
the sister chromatids are correctly attached to the spindle microtubules
before the cell enters the irreversible anaphase stage.
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Figure 2.1:Cell cycle checkpoints
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