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Cancer

A cancer is an abnormal type of tissue growth in


which cell divide in an uncontrolled, relatively
autonomous fashion, leading to a progressive
increase in the number of dividing cells.
The resulting mass of growing tissue is called a
tumor or neoplasm.
Cancers can originate in almost any organ. They
are grouped depending on the cell type:

1. Carcinomas (most prominent @90%) arise
from epithelial cells (from external and
internal body surfaces).
2. Sarcomas arise from supporting tissues (bone,
cartilage, fat, muscle etc.)
3. Lymphomas and leukemia arise from cells of
blood and lymphatic origin.
Key properties of cancer cells:


1. The ability of cells to proliferate in an
uncontrolled fashion and
2. The ability to spread through the body.
It is the combination of these actions that
makes cancers dangerous.
Tumors are produced by uncontrolled cell
proliferation in which the balance between
cell division and cell differentiation is
disrupted
Comparison of normal and tumor growth in the
epithelium of the skin. The basal layer of epithelial cells
grow more than the surrounding cells to form a tumor
Based on differences in their growth patterns,
tumors are classified as either benign or
malignant.

Benign tumor grows in a confined local area and is rarely
dangerous whereas malignant tumor is capable of invading
surrounding tissues, entering blood stream and spreading to
distant parts of the body which make it a serious health
hazard.
Benign malignant
Cancer cell proliferation is anchorage-
independent and insensitive to population
density


Normal cell dont grow well in liquid or semi solid
medium and require a supporting surface to grow in
culture.

Cancer cells can grow well in liquid or semi-solid
media therefore exhibit anchorage independent
growth
Tumor cells
Monolayer stage
Piling up on top of each
other
A
B
Tumor cell are insensitive to population density
In culture, most normal cells divide until a monolayer is formed. Cancer
cells "pile up".
Cancer cells are immortalized by
mechanism that maintain telomere length
Normal cell divide about 50-60 times when placed in culture, then stop
dividing. Whereas HeLa cell dividing more than 18,000 times with no
sign of stop
Cancer cell Normal cell
Telomerase enzyme add DNA
sequences at the end of the
chromosome of tumor cells
thus maintaining the telomere
length
Abnormalities in signaling pathway, cell cycle
controls and apoptosis contribute to uncontrolled
proliferation

If the normal cell grown under suboptimal conditions
(insufficient growth factors, inadequate nutrients),
the cells become arrested at the restriction point (G1
into S phase) and stop dividing.

In compare cancer cells continue to proliferate even
in the extreme adverse condition rather than
arresting at G1 phase.
How cancer spreads?
Angiogenesis is growth of blood vessels
in the surrounding tissues, required for
tumors to grow beyond a tiny localized
clump of cells.

Tumor cell release signaling molecules
that trigger Angiogenesis includes
VEGF and FGF.
Angiogenesis
Experiment illustrating the requirement for Angiogenesis
Molecules that regulate angiogenesis
includes both activators and inhibitors.
Activators Inhibitors
VEGF (vascular
endothelial growth
factor)
Angiostatin
FGF (fibroblast growth
factor)
Endostatin
Thrombospondin
Spreading of cancer by invasion and
metastasis is a complex and multistep
process

1. Cancer cells migrate and penetrate
into adjacent tissues and vessels.
2. Transport via circulatory system and
3. Reinvasion and growth at a distant
sites to form a tumor.
Invasion and Metastasis
Invasion and metastasis processes require
changes in cell adhesion molecule (E-
cadherin), motility (signaling molecules as
chemo-attractants) and the production of
proteases that degrade protein-based
physical barriers to cell movement.
What Causes Cancer?
Causes of Cancer

Chemicals
Diet and obesity
Infection
Radiation
Heredity
Physical agents
Hormones


Factors Believed to Contribute to Global Causes of Cancer
Cigarette Smoking
Tobacco smoking is associated with many forms of
cancer, and causes 90% of lung cancer in US
Carcinogens
Ames test to
identify
potential
carcinogens
Viral Factors
Herpes-related viruses may be involved in the
development of leukemia, Hodgkins disease,
cervical cancer, and Burkitts lymphoma
Epstein-Barr virus, associated with
mononucleosis, may contribute to cancer
Human papillomavirus (HPV), virus that causes
genital warts, has been linked to cervical cancer
Helicobacter pylori causes ulcers which are a
major factor in the development of stomach
cancer
Oncogene and Proto-oncogene
Oncogenes are a gene whose presence
can trigger the development of cancer.

Some oncogene are introduced by
cancer causing virus, whereas other
arise by mutation from normal cellular
gene.

Either case gene product stimulate
excess cell proliferation.
Oncogenes arise by mutation from normal cellular
genes called proto-oncogenes.

Proto-oncogenes are not harmful genes, they are
normal cellular genes that play role in regulation of
cell growth and survival.

They become oncogene when their structure are
disrupted by mutation, the mutant form cause
cancer.
Mutation that convert proto-oncogenes into
oncogenes are created by several mechanism:

1. Point Mutation
2. Gene Amplification
3. Chromosomal translocation
4. Local DNA rearrangements
5. Insertional Mutagenesis
Most oncogenes codes for components for growth
signaling pathway

1. Growth factors
2. Receptors
3. Plasma membrane GTP-binding proteins
4. Non-receptor Protein kinases
5. Transcription factors
6. Cell cycle or cell death regulators


Tumor Suppressor genes
Fusion cancer cell with normal cell
Tumor suppressor genes are genes
whose loss or inactivation can lead to
cancer


The RB tumor suppressor gene was
discovered by studying families with
hereditary retinoblastoma
G1 S phase
Disruption of RB protein removes restrain mechanism
and open door to uncontrolled proliferation
The p53 tumor suppressor gene is the most
frequently mutated gene in human cancer
The DNA damage
checkpoint is
regulated by p53,
"the Guardian of
the Genome"!

The role of p53 is to
protect cells from
the effects of DNA
damage.
What will happen if p53 gene get disrupted?
Upon inactivation of p53 pathway
results cancer development by allowing
the survival and reproduction of cells
containing damaged DNA
Both Rb protein and p53 protein are
the target for cancer causing virus
Human papillomavirus (HPV)