Cancer Biology

Geeta Mohan
 Cancer Biology
The word ‘cancer’ is derived from the word, ‘carcinos’
the Latin word for crab. It was Celsus who translated
the word. The word is a general term for a group of
diseases that can affect all parts of the body.
Cancer is a group of diseases involving abnormal cell
growth with the potential to invade or spread to other
parts of the body. There are more than 100 types of
cancer, including breast cancer, skin cancer, lung
cancer, colon cancer, prostate cancer, and lymphoma.
Symptoms vary depending on the type.
Cancer Biology

• In all animals there is a balance between the cells

that perish and the cells that are formed. This
maintains the number of cells more or less
constant in any organ.
• The cells that divide form numerous cells called
clones, which are not required by the body. The
cells form a mass or tumour called neoplasm.
• The definition of a tumor is a mass of quickly and
abnormally growing cells.
Cancer Biology

• The tumors are of two types

• The tumor that stops dividing after sometime and
does not invade into the surrounding tissues is said
to be benign.
• If the tumor continues to grow and becomes invasive
or spreads to the neighboring tissue it is said to be
malignant.
• Malignant tumors are referred to as ‘cancer’. The
tumor grows without undergoing any differentiation
and this condition is called anaplasia
Cancer Biology

Metastasis
• The malignant tumor cells from one organ can break
free, enter into the blood stream and are carried to
another site where they continue to grow. This
process of a primary tumor giving rise to a secondary
tumor is called metastasis.
• Metastasis is defined as the stage in which cancer
cells are transported through the blood stream or
lymphatic system.
• Such tumors are difficult to treat, as they are able to
spread to other parts of the body and cannot be
completely removed surgically.
Cancer Biology
The process of metastasis occurs in many steps
• In the first step the cancer cells break through the
basement membrane or capsule and invade the
surrounding tissue.
• The cells will detach from the main mass and be picked up
by the lymphatic or vascular circulation.
• The cells that are now circulating will lodge in another
tissue for some time. For example the cells traveling
through the lymphatic system they often lodge in a lymph
node. The cells that are circulating in the blood stream
must adhere or stick to the endothelial cells and pass
through the vessel wall into any organ or tissues.
• They produce enzymes to make the other organ or tissue
receptive and lodge themselves in a new
microenvironment.
• The must establish a blood supply to bring oxygen and
nutrients by secretion of angiogenesis factors.
All the above steps will happen provided the cells are not
killed by the immune system.
Cancer Biology

CLASSIFICATION OF CANCER
• There are various types of cancers that are known
to affect the human body. Malignant tumours or
cancers can be classified in two ways
• Based on the tissue, from which they are derived.
• Based on the part of the body where it first
develops.
Cancer Biology
Based on the tissue from which they are derived they are classified
as follows
• Carcinomas :The tumors arising from epithelial cells, either the
endoderm or ectoderm are said to be carcinomas. 80% of the
tumors belong to this category. The carcinomas appear on the
skin and in the lining of internal organs or glands. Example the
cancer of colon, lungs, prostate and breast cancer.
• Sarcomas : The tumors arising from the mesodermal connective
tissue are said to be sarcomas. They are less frequent. Example
the cancer of the bone, muscles and cartilage.
• Lymphoma and leukemia : The tumor of the haemopoietic cells in
the bone marrow are said to be lymphoma. The proliferation of
the leukocytes is called leukemia or blood cancer.
• Mesothelioma :The tumor of the mesothelial cells lining the
peritoneum and the pleura.
• Glioma : The tumors of the glial cells found in the brain.
• Germ cell tumors : The tumors are formed in the testis or ovary.
• Choriocarcinomas : The tumors in the placenta.
Cancer Biology
Based on the part of the body where it first develops they are classified
as follows
• Skin cancer : This is one of the most common forms of cancer that
effects the world’s population. The cancer of the skin is common as it
is exposed to the radiation of the sun and also to a number of
chemicals that are pollutants or in cosmetics.
• Lung cancer : is seen mostly in smokers and those working in
factories who are exposed to chemical fumes and dust. Lung cancer
also seems to be on the rise in non-smokers due to air pollution.
• Oesophageal cancer : is common among those who drink very hot
beverages and smoke, and also in alcoholics.
• Stomach cancer and intestinal cancers : is seen in those populations
who live on preserved food and have a low intake of fresh food in their
diets. The stomach cancer is also caused due to chronic ulcers,
consumption of alcohol and smoking.
• Liver and pancreatic cancer : Liver cancer is common in those who
are prone to infection such as Hepatitis. Pancreatic cancers are seen
as secondary tumours that are derived from stomach or duodenal
regions.
• Colon cancer : occurs in those who have a deficiency of dietary fibres
in their food. Those who live only on high fat foods, bakery products,
meat and processed food, ice creams, deserts etc and do not
consume leafy vegetables are prone to colon cancer.
Cancer Biology

• Breast cancer : is the most common cancer that affects

one in every five women. The women who have a high
risk of getting breast cancer are those who have
children late in life, do not have children, use
contraceptives, and consume high fat food and those
who do not exercise. Breast cancer is also inherited.
• Cervical cancer : is the cancer seen in the cervix of the
uterus. This cancer is related to poor hygiene and poor
diet therefore occurs in women who belong to the
poorer section of the society.
• Prostate cancer : is the most common cancer in older
males. The prostate gland develops tumours that can
become malignant. It causes a lot of complication in
the urinary system as it tend to block the urethra which
it surrounds blocking the passage of urine or it presses
down on the urinary bladder causing incontinence.
 Cancer Biology
The cancers of different organs are named according
to the organ and using the suffix, ’oma’.
The term, ‘oma’ means swelling, the cancerous
swelling is called carcinoma. Example, the cancer of
the liver is called hepatocarcinoma and the benign
tumour of the smooth muscles of the uterus is called
leiomyoma commonly called fibroids.
Galen used the word’ ‘oncos’ to describe all tumours
from which the modern word ‘Oncology’ has been
derived. Oncology is the study of cancer.
Cancer Biology
GENERAL PROPERTIES OF CANCER CELLS
1) Uncontrolled Proliferation : Proliferation is seen in all cells even
in cancer cells. But the normal cells stop dividing after a
certain size is attained. The cancer cells show uncontrolled
proliferation.
The cell cycle comprises of four stages, called M, G1, S, and G2. M
is the mitotic or division phase and is composed of four sub
phases: prophase, metaphase, anaphase, and telophase. S is the
DNA synthesis phase, when each gene on each chromosome is
exactly duplicated in preparation for mitosis. The S and M phases
are separated by two gaps called G1 and G2. G0 is a resting or non
dividing stage . The shift from one phase to the next is also
regulated by proteins called cyclins. The cyclins are regulated by
cyclin-dependent kinase. The gene coding for the regulatory
proteins are protooncogenes. If mutations occur in the
protooncogenes causing over expression of the protooncogenes an
uncontrolled proliferation or cell division occurs. Protooncogenes
promote cell division by production of hormones which encourages
mitosis. The cells show an altered response to factors that control
growth and differentiation.
Cancer Biology
2) Unlimited Growth Potential : Due to Overabundance of
Telomerase - A normal cell has a limited ability to replicate
its DNA allowing the cell to divide only a few times. Each
time the chromosome replicates, the ends called telomeres
shorten. In the cells that are growing, the ends or telomeres
are replaced by an enzyme called telomerase. In cancer cells
there is an abundance of telomerase which activates the
cells to divide uncontrollably.
3) Self Sufficiency of Growth Factor : Normal cells are
stimulated by external growth factors to undergo division.
The synthesis of these growth factors is inhibited by normal
cell regulation and the cells stop dividing. Cancer cells have
lost the need for positive growth factors, therefore they
divide whether these factors are present or absent. The
cancer cells do not behave as part of the tissue. They are
autonomous or become independent cells as they show a
self-sufficiency of growth factor.
Cancer Biology
4) Loss of Contact Inhibition to Slow Growth : Normal
cells show contact inhibition, which means their ability
to divide and grow is curbed or inhibited by the contact
with other neighbouring cells. Thus the cells divide till
they come in contact with the other cells or just to fill a
gap. This important feature of normal cells is lost in
cancer cells. The cells will continue to grow even after
they touch other cells, they will even grow over the other
cells forming a large mass of cells. When the cancer
cells are grown in a culture medium they divide even
after coming in contact with the other cells and continue
to grow over them.
5) Lack of Adhesion Requirement for Growth : Normal
cells have the ability to adhere or stick to one another
and maintain the integrity of the tissue. For example,
lung cells stick to lung cells. The tendency of cells to
stick together is called adhesion. Cancer cells show a
lack of adhesion that gives them the ability to “break
away” from the original mass of cells and allow the cells
to spread.
Cancer Biology

6) Inability to Differentiate Completely : Cells and tissues

differentiate to become adult cells that are, ‘mature’ and it
becomes specialized and takes up a specific function. This
is called differentiation. The cellular differentiation
process goes from immature to mature. It also loses its
ability to divide. An undifferentiated cell maintains its stem
cell like character and is able to reproduce. It does not
take up any normal function. Cancer cells are like
undifferentiated cells and maintain their reproductive
capability.
7) Evading Apoptosis : Normal cells, divide, age and die,
and are replaced by new cells in a regulated or controlled
and orderly manner. Apoptosis is called normal or
programmed cell death. Normal cells can divide only about
fifty times before they die. In the normal process of
apoptosis, the DNA is first destroyed and then the cell
automatically dies. The cancer cells are able to dodge or
evade apoptosis even though their DNA has undergone
mutation and are faulty.
Cancer Biology
8) Ability to invade neighbouring tissues and to build
metastases at distant sites :
• The cancer cells arise from single cells that have escaped
the normal growth control factors of the body. The cells have
lost the property of contact inhibition and adhesiveness. As
growth progresses the cells push through the basement
membrane and invade other tissues.
• When some cells become loose and do not exhibit
adhesiveness, they are picked up by the lymph and carried to
lymph nodes or may enter capillaries and come into the blood
stream.
• If the cancer cells can escape the immune system they
continue to grow in the new site where they are lodged. Thus
a metastasis is formed. Normally cancer patients die due to
metastasis.
9)Ability to Promote the Growth of Blood Vessels
(Angiogenesis) : The cells of a tumour or cancer need nutrients
and oxygen to grow and survive. This is possible only if they
are supplied with blood. They produce certain chemicals that
stimulate the formation of new blood vessels. The process of
formation of new blood vessels is called angiogenesis. This
property of the cancer cells is what makes them grow and
spread and establish metastasis at new sites.
Cancer Biology

10) Immortality : The cancer cells do not

differentiate but retain their stem cell condition,
therefore they are capable of dividing indefinitely. In
the lab when a culture medium with nutrients is
provided the cells divide endlessly this gives them
the property of immortality. (A HeLa cell, also Hela
or hela cell, is an immortal cell line used in medical
research. The cell line was derived from cervical
cancer cells taken from Henrietta Lacks, who died
from her cancer in 1951).
Cancer Biology

• CARCINOGENS :Cancer occurs in people

belonging to any age group, but is most commonly
seen in those who are in their middle age and
older people. Cancer is common in both men and
women. Among women breast cancer and
cervical cancer is common while men suffer from
prostate cancer. There are several reasons for the
cause of cancer. The development of cancer
involves several steps and is usually caused by
more than one single factor. Carcinogenesis or
the process of initiation of cancer could be
triggered due to various factors both intrinsic and
extrinsic. The factors that cause cancer are
called carcinogens.
Cancer Biology
The Intrinsic Factors : The intrinsic factors are the inherent factors within
the cells that can cause a transformation such as
• The genes that have mutated and confirmed immortality to these cells.
Cancer is considered to be the disease of the genes. The mutations in
the proto oncogenes or in the tumor suppressor genes are the main
reasons for carcinogenesis. The over expression of the proto oncogenes
allows uncontrolled cell division and the mutated tumor suppressor
genes can no longer control the excess growth of cells. Mutations can
occur during cell division.
• Chromosomal translocations are also responsible, for example the
chronic myelogensous leukemia cells show a translocation of a
fragment of chromosome number 9 into chromosome number 22, which
is called the Philadelphia chromosome.
• There are enough evidences that suggest a genetic predisposition in the
occurrence of cancer. Many cancers are inherited, such as the cancer
of the breast and colon. The gene for breast cancer has been identified
as BRCA 1 and BRCA 2. A woman with any of the two genes has 80%
risk of getting breast cancer before the age of 70. DNA fingerprinting of
the parent and the children helps in detection of such genes. However
the expression of the genes are controlled and regulated by the body.
The onset of cancer cannot be predicted.
Cancer Biology
The extrinsic factors that cause cancers are called carcinogens.
Carcinogens are agents that cause cancer. Carcinogens are
broadly classified as follows
• Physical carcinogens
• Chemical carcinogens and
• Biological carcinogens
a) Physical Carcinogens : Physical carcinogens include
fibers, particulate matter, hard and soft synthetic materials and
gels. Some physical carcinogens are naturally occurring, while
others are synthetic. Physical carcinogens are highly variable in
their chemical structure, and many of them are poorly
understood. Furthermore, the method by which they cause
cancer is even more mysterious. No specific pathway has been
isolated that correctly identifies the way physical agents cause
cancer.
• Physical agents such as radiations are known to be
carcinogens. Radiations are physical mutagens that induce
mutations. The radiations differ in their wavelength and their
energy level.
 Cancer Biology
• Physical agents such as radiations are known to be carcinogens.
Radiations are physical mutagens that induce mutations. The radiations
differ in their wavelength and their energy level.
• The radiations are generally of two types based on their effects, they are
• Ionizing
• Non-ionizing radiations
1) Ionizing radiations
• Ionizing radiations are those that have a high penetrating power and can
induce mutations. For examples, gamma rays and X-rays. These ionizing
radiations cause breaks in the backbone of the DNA. They can cause
chromosomal mutations such as breaks, restitution, deletion, inversion
etc. This is the reason physicians never use X-rays on pregnant women.
2) Non-ionizing radiations
• Radiations cause a lot of harm. On exposure to radiation the skin is
affected, it turns red and lesions may appear. It causes skin cancer. High
doses of radiations effect internal organs that are soft like liver, kidneys
etc may get damaged. The bones, muscles and nerves are definitely
affected. The bone marrow is destroyed and as a result the production
of blood cells is affected.
Cancer Biology

b) Chemical Carcinogens
Several chemicals that cause cancer or initiate
carcinogenesis have been identified over the years and
researchers have confirmed their effects. Chemicals that
are carcinogenic are seen in the environmental pollutants,
food and food products, cosmetics and dyes, tobacco
smoke, pan and gutka, and in the hormones that are used
in birth control pills.
i.Environmental pollutants: effluents that are let off into
the nearby water bodies, smoke and particulate matter in
the air and wastes such as metals, acids, alkalis,
alcohols, phenols, cyanide compounds, detergents,
arsenic etc in the soil. Many of the chemical pollutants
are carcinogenic such as, paints and dyes, arsenic,
asbestos, chromium, lead, nickel, iron etc. The products
of coal and petroleum, polyvinyl chloride compounds, are
well known carcinogens.
 Cancer Biology

ii. Food and food products

• Food that is normally thought to be safe is contaminated with carcinogens.
Food colourings, food flavours, additives, stabilizers in jellies, sweets and
ice creams, are carcinogenic. Acrydine dyes like acrydine orange give the
characteristic yellow or orange colour to the sweets.
• The preservatives used in pickles, jams, jellies, canned food, and the
pesticides used to preserve the dhals, grains, rice and even wheat flour etc
are carcinogenic.
• Few foodstuffs that contain active agents considered as carcinogenic are
listed below
• Alcohol is metabolized to acetaldehyde
• Black pepper contains piperine and safrole
• Coffee, tea and chocolate contain caffeine and theobromine
• Food cooked in gas oven contains nitrosamine
• Grilled and barbecued chicken, beef etc contain heterocyclic amines,
nitrosamines.
• Mould on peanuts, cheese, butter and bread contain aflatoxins
Cancer Biology

• Chemicals in cosmetics - Sun screen, hair dye

• Hormones in contraceptive pills and hormones administered
during therapy -contain progesterone and estrogen.
Prolonged use causes progesterone and estrogen increases
the chances of uterine cancer. Prolonged use of pills makes
women prone to uterine, ovarian and breast cancer.
• Tobacco smoke is carcinogenic : Smoke contains chemical
compounds like nicotine, tar, polycyclic hydrocarbons etc ,
which are identified as carcinogens. Cigarette smoke
irritates the lining of the pharynx, trachea and bronchi.
• Chemicals in the work place :Workers in the industries such
as, chemical and paint factories etc are exposed to
chemicals that are carcinogenic. Soot and coal tar are
carcinogenic. Factory workers exposed to arsenic develop
skin cancer.
Cancer Biology

• Biological carcinogens are the living carcinogens such as

viruses. It is a known fact that many viruses cause cancer.
They are generally called onco virus. The virus could be a
DNA virus or a retro virus which is a RNA virus
• Examples of viruses that cause cancers are as follows,
• The cervical cancer of the neck of the uterus is caused by
the
Papilloma virus.
• The Epstein –Barr virus causes the cancer of the lymphatic
system called Burkitt’s lymphoma
• Hepatitis B virus and aflatoxins cause liver cancer.
• Herpes type viruses are observed in several cancers such
as chronic leukemia and cancer of the uterus.
 Structure Variations in the Cancer Cells

• The cancer cells show a variation in their cell structure and cell organelles.
• The plasma membrane of the cancer cells is different. The plasma membrane is the
dynamic membrane which has on it receptors for hormones and enzymes. The
receptors for the growth hormones and differentiation are altered. Thus the cells do
not differentiate and show uncontrolled growth.
• The plasma membrane has on it surface markers which are glycoproteins Changes in
the surface markers are seen which does not allow the cell to be recognized by the
immune system and allows metastases.
• The nuclear membrane and nucleolus are different. The membrane show deep folding
and bleb formation.
• The mitochondria increase in number; they however appear irregular and swollen and
possess fewer cristae.
• In few cells the golgi complex seem to be poorly developed except in secretory tissues
or glands where they are more in number and highly developed.
• The cells normally have a network of minute fibres and filament that allow mobility
and determine the shape of the cell. The microfilaments are reduced and disorganized
in a cancer cell. Example a fibroblast that is spindle shape become more compact and
changes its appearance.
• There is an enormous endoplasmic reticulum network in the cells and increase in the
amount of ribosomes as the cells are involved in making proteins rapidly to cope with
the tremendous rate of cell division. Polysomes are found in abundance.
Biochemical and Metabolic Variations in Cancer Cells
The cancer cells show an altered metabolism as compared to the normal
cells.
Cancer cells exhibit more rapid rates of uptake of nutrients than their
normal counterparts, indicating changes in the activity of membrane
transport mechanisms.
The cell surface shows an increase in number of negative charges
because of a large amount of glycosaminoglycans .
The cells show a loss of gap junctions and show electrical
uncoupling. This makes them independent and lose the capacity of
adhesion and contact inhibition.
The altered plasma membrane shows an easy diffusion of
receptors in the lipid bi layer due to the disorganization of
microfilaments.
There is an alteration in the content of glycolipid and glycoprotein
and there is a reduction of gangliosides and in their ability to
synthesize enzymes.
Certain proteins disappear in the cell membrane because of which
there is an increase in the sugar uptake.
 Biochemical and Metabolic Variations in Cancer Cells

• Certain proteins disappear in the cell membrane because of which there is an increase in the sugar
uptake.
• Cancer cells release the intracellular enzymes into the surrounding medium as the cell becomes,
‘leaky’ due to a faulty cell membrane.
• Cancer cells carry on them new antigens different from what is seen on normal cells.
• The cancer cells produce enzymes or proteases that converts plasminogen to plasmin. Plasmin can
dissolve blood clots and can strip the cell membrane of the surface proteins that are exposed.
• The cancer cells show a different method of metabolizing iron and trace metal ions. The normal
cells have the glycoprotein called transferrin (high molecular weight) that transports iron into the
cell, and the iron binds to ferritin and is made use of in the cytochrome enzyme system. The cancer
cells secrete a low molecular weight glycoprotein, a growth factor similar to siderophore into the
medium. This has a higher affinity to iron and forms a complex outside the cell, which is then
transported inside easily. The cancer cells therefore show a faster rate of uptake of iron needed
for their rapid cell division.
• Fibronectin is a high molecular weight glycoprotein that is involved in cell adhesion between cells,
and between the cells and substratum. It also plays an important role in the morphology of the cell
as it influences the organization of the cytoskeleton, as well as their migration and locomotion. The
cancer cells show a reduction in the fibronectin content. This is the reason for the cancer cells to
change their shape, to be able to break away form the primary site and to move to a secondary
site.
• In cancer cells the division of chromosomes is highly faulty or full of errors. This is seen in the
karyotype of the cells. The activity of certain regulatory proteins associated with chromosomes
may be altered during malignancy. Thus the cancer cells exhibit abnormal patterns of protein synt
PREVENTION

• Cancer is caused by several agents such as physical, chemicals and biological

as mentioned above. It is also caused due to faulty genes and chromosomal
translocation. As the onset of cancer cannot be predicted, one can only be
alert to signs and symptoms such as,
• The appearance of an abnormal lump in any part of the body.
• Unusual bleeding and secretion from the breast or vagina.
• The change in shape of the breast or nipples.
• The ulcer that does not heal.
• Persistant cough.
• Change in bowel habits.
• Hyper acidity condition and indigestion even after treatment with antacids.
• Fever that reccurs often.
• Nausea, hypertension and dizziness is a sign of brain tumour. Sometimes a
stroke can also occur.
Prevention of cancer

• Eating healty foods that are rich in fibres, anti oxidants is

important. The diet should be balanced and must contain,
greens, vegetables, fruits, and white or lean meat. A good diet is
important to prevent cancer. A diet rich in vitamins C and E
prevents cancer.
• Avoiding excessive intake of fatty foods such as butter, ghee,
fried food and bakery products.
• Avoiding excessive consumption of alcohol and alcohoilc drinks.
• Avoiding smoking totally.
• Exercising regularly to prevent obesity.
• Regular self examination of the breast.
• Being alert to symptoms that are abnormal.
• Making medical check ups a routine every 2-3 years after 30
years of age
Cancer Biology

Credits :
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