Notes on Cancer

Contents:

1. Notes on the Subject-Matter of Cancer

2. Notes on the Meaning of Cancer

3. Notes on the Types of Cancer

4. Notes on the Development of Cancer

5. Notes on the Characteristics of Cancer Cells

6. Notes on the Causes of Cancer

7. Notes on Oncogenes

8. Notes on Proto-Oncogene

9. Notes on Tumour Suppressor Genes

10. Notes on Prevention and Treatment of Cancer

Notes # 1. Subject-Matter of Cancer:

In multicellular organisms, cell division is a normal process. Cells divide for growth, for the
development of organs, for healing of wounds and also for the replacement of older and damaged
cells. Cell division is a very complex process which is controlled by a regulatory mechanism at both
molecular and cellular level.

Again, in higher multicellular organism, each and every cell belongs to a particular type of tissue like
epithelial tissue, connective tissue muscular tissue etc.

Hence, when a cell of a specific tissue divides, it normally produces its own kinds of cell of the tissue
to which it belongs. It never produces the cells of other tissues. Therefore, the process by which cells
achieve this specification and specialisation is known as cellular differentiation. Differentiation of cell
begins during embryonic gastrulation stage and continues through tissue formation.

Actually differentiation has a genetic basis and the process results from the interaction of the nucleus
and the cytoplasm. After the cells become well- differentiated, they cannot go back normally to the
undifferentiated stage unless disturbed internally or externally.

Therefore, in multicellular organism, the cell division, differentiation and survival of individual cells
are carefully regulated to meet the needs of the organism as a whole. When this regulation is lost
due to any reason, the cells behave unusually and defy their control mechanism.

Then the cells grow and divide in an uncontrolled manner ultimately spreading throughout the body
and interfering with the functions of normal tissues and organs. As a whole, this condition leads to
cancer. Cancer develops from defects in fundamental regulatory mechanisms of the cell.
Notes # 2. Meaning of Cancer:

Cancer is a non-infectious disease. It starts at the molecular level of the cell and, ultimately affects
the cellular behaviour. Generally, it can be defined as uncontrolled proliferation of cells without any
differentiation.

Notes # 3. Types of Cancer:

Cancer is a large class of diverse disease. All types of cancer can result from uncontrolled cell growth
and division of any of the different kinds of cells in the body. So there are more than a hundred
distinct types of cancer which vary in their behaviour and response to treatment.

The uncontrolled cell growth produces a mass of cells which are called tumours or neoplasm
tumours may be benign or malignant. A benign tumor remains confined to its original location. They
do not invade the surrounding normal tissues. They do not spread to distant body sites.

The most common example of tumour is the skin wart. A benign tumour consists of closely
resembles normal cells and may function like normal cells. Generally benign tumours are harmless
and can usually be removed surgically. However, these tumours may sometimes become quite
harmful if they are located in organs like brain and liver.

A malignant tumour does not remain confined to its original location. They are capable of both
invading surrounding normal tissue and spreading throughout the body via the circulatory or
lymphatic systems. Malignant tumours become life-threatening if, they spread throughout the body.

Only malignant tumours are properly designated as cancers. The cells of malignant tumour are
derived from single cell, thus they are monoclonal in character. Malignant tumour is composed of
aberrant cells. They behave like embryonic type, undifferentiated, having irregular, large nucleus, and
deficient of cytoplasm. Malignant tumours are generally classified into four main types on the basis
of cell type from which they arise.

(i) Carcinomas:

It includes approximately 90% of human cancer. This type is principally derived from epithelial cells
of ectoderm and endoderm. The solid tumours in nerve tissue and in tissues of body surfaces or their
attached glands are example of carcinomas. Cervical, breast, skin and brain carcinomas are
developed from malignant tumour.

(ii) Sarcomas:

Sarcomas are solid tumours of connective tissues such as muscle, bone, cartilage and fibrous tissue.
This type of malignant tumours are rare in human (about 2% of human cancer).

(iii) Lymphomas:

It is a type of malignancy in which there is excessive production of lymphocytes by the lymph nodes
and spleen. It accounts for approximately 8% of human cancers. Hodgkin’s disease is an example of
human lymphoma.

(iv) Leukemia’s:
Study Notes on Cancer

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Study Notes on Cancer:- 1. Subject-Matter of Cancer 2. Meaning of Cancer 3. Types 4. Development

5. Characteristics of Cancer Cells 6. Causes 7. Oncogenes 8. Proto-Oncogene 9. Tumour Suppressor
Genes 10. Prevention and Treatment.

Contents:

1. Notes on the Subject-Matter of Cancer

2. Notes on the Meaning of Cancer

3. Notes on the Types of Cancer

4. Notes on the Development of Cancer

5. Notes on the Characteristics of Cancer Cells

6. Notes on the Causes of Cancer

7. Notes on Oncogenes

8. Notes on Proto-Oncogene

9. Notes on Tumour Suppressor Genes

10. Notes on Prevention and Treatment of Cancer

Notes # 1. Subject-Matter of Cancer:

In multicellular organisms, cell division is a normal process. Cells divide for growth, for the
development of organs, for healing of wounds and also for the replacement of older and damaged
cells. Cell division is a very complex process which is controlled by a regulatory mechanism at both
molecular and cellular level.

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Again, in higher multicellular organism, each and every cell belongs to a particular type of tissue like
epithelial tissue, connective tissue muscular tissue etc.

Hence, when a cell of a specific tissue divides, it normally produces its own kinds of cell of the tissue
to which it belongs. It never produces the cells of other tissues. Therefore, the process by which cells
achieve this specification and specialisation is known as cellular differentiation. Differentiation of cell
begins during embryonic gastrulation stage and continues through tissue formation.

Actually differentiation has a genetic basis and the process results from the interaction of the nucleus
and the cytoplasm. After the cells become well- differentiated, they cannot go back normally to the
undifferentiated stage unless disturbed internally or externally.
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Therefore, in multicellular organism, the cell division, differentiation and survival of individual cells
are carefully regulated to meet the needs of the organism as a whole. When this regulation is lost
due to any reason, the cells behave unusually and defy their control mechanism.

Then the cells grow and divide in an uncontrolled manner ultimately spreading throughout the body
and interfering with the functions of normal tissues and organs. As a whole, this condition leads to
cancer. Cancer develops from defects in fundamental regulatory mechanisms of the cell.

Notes # 2. Meaning of Cancer:

Cancer is a non-infectious disease. It starts at the molecular level of the cell and, ultimately affects
the cellular behaviour. Generally, it can be defined as uncontrolled proliferation of cells without any
differentiation.

Notes # 3. Types of Cancer:

Cancer is a large class of diverse disease. All types of cancer can result from uncontrolled cell growth
and division of any of the different kinds of cells in the body. So there are more than a hundred
distinct types of cancer which vary in their behaviour and response to treatment.

The uncontrolled cell growth produces a mass of cells which are called tumours or neoplasm
tumours may be benign or malignant. A benign tumor remains confined to its original location. They
do not invade the surrounding normal tissues. They do not spread to distant body sites.

The most common example of tumour is the skin wart. A benign tumour consists of closely
resembles normal cells and may function like normal cells. Generally benign tumours are harmless
and can usually be removed surgically. However, these tumours may sometimes become quite
harmful if they are located in organs like brain and liver.

A malignant tumour does not remain confined to its original location. They are capable of both
invading surrounding normal tissue and spreading throughout the body via the circulatory or
lymphatic systems. Malignant tumours become life-threatening if, they spread throughout the body.

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Only malignant tumours are properly designated as cancers. The cells of malignant tumour are
derived from single cell, thus they are monoclonal in character. Malignant tumour is composed of
aberrant cells. They behave like embryonic type, undifferentiated, having irregular, large nucleus, and
deficient of cytoplasm. Malignant tumours are generally classified into four main types on the basis
of cell type from which they arise.

(i) Carcinomas:

It includes approximately 90% of human cancer. This type is principally derived from epithelial cells
of ectoderm and endoderm. The solid tumours in nerve tissue and in tissues of body surfaces or their
attached glands are example of carcinomas. Cervical, breast, skin and brain carcinomas are
developed from malignant tumour.

(ii) Sarcomas:
Sarcomas are solid tumours of connective tissues such as muscle, bone, cartilage and fibrous tissue.
This type of malignant tumours are rare in human (about 2% of human cancer).

(iii) Lymphomas:

It is a type of malignancy in which there is excessive production of lymphocytes by the lymph nodes
and spleen. It accounts for approximately 8% of human cancers. Hodgkin’s disease is an example of
human lymphoma.

(iv) Leukemia’s:

This type of malignancy arises from the blood forming cell. Leukemia’s are commonly known as
blood cancer. Leukemia’s are neoplastic growth (uncontrolled cell growth at the cost of remaining
cells) of leucocytes or WBC.

They are characterised by excessive production of WBC of the blood. The name leukemia is derived
from Greek leukos (white) + haima (blood) the massive proliferation of leukemia cells can cause a
patient’s blood to appear milky.

In addition to the types of cancer mentioned above, cancers are further classified according to tissue
of origin, for example lung cancer, breast cancer, and the type of cells involved, for example fibro
sarcoma arises from fibroblasts, erythromoid leukemia’s from precursor of erythrocytes. Although
there are many kinds of cancer, the four most common cancers are those of prostrate, breast, lung
and colon/rectum.

Notes # 4. Development of Cancer:

The development of cancer is a multistep process in which cells gradually become malignant through
a progressive series of alternations. This process involves mutation and selection for cells with
progressively increasing capacity for cell division, survival, invasion and metastasis (spread of cancer
cells through the blood or lymphatic system to other organ sites).

The first step in the process is when a single cell within a tissue of the organ concerned is genetically
modified. The modified cell divides rapidly, although surrounding cells do not— and a mass of
tumour cells forms.

These cells constitute a clone where cells are identical in terms of structure, characteristics and
function. Rapid cell proliferation leads to the tumorous outgrowth or adenoma or polyp. This tumour
is still benign.

Tumour progression continues as additional mutation occur within cells of tumour population. Some
of these mutations give a selective advantage to the cell such as rapid growth and the descendants
of a cell bearing such a mutation will consequently become dominant within the tumour population.

This process is known as clonal selection. Clonal selection continues throughout tumour develop-
ment and, consequently, tumour become more and more rapid, growing and increasingly malignant.
The tumour cells, by their rapid proliferation, invades the basal lamina that surrounds the tissue.

Then tumour cells spread into blood vessels that will distribute them to other sites in the body. This
is known as metastasis. If the tumour cells can exit from the blood vessels and grow at distant site,
they are considered malignant (Fig. 23.1).
Notes # 5. Characteristics of Cancer Cells:

The uncontrolled growth of cancer cells results from accumulated abnormalities affecting many of
the cell regulatory mechanisms. The process of cell change in which a normal cell loses its ability to
control its rate of division and thus becomes a tumour cell is called cell transformation.

Cancer cells shows some typical characteristic properties that are absent in normal cells. Sometimes
cancer cell properties are just opposite to the properties of normal cell. Cancer cells in vivo differ
from their normal counterparts in several respects. Some characteristic properties of cancer cells can
also be demonstrated by cell culture in vitro.

(i) Immortalization:

Normal cell culture do not survive indefinitely For example, human cell culture die after about 50
generations. On the other hand, transformed cell cultures can go on indefinitely and remain
immortal if the nutrition is provided and overcrowding avoided.
(ii) Loss of Contact Inhibition:

Normal cells growing in tissue culture tend to make cell contacts by adhesion to neighbouring cells.
At the points of adhesion some kind of electron-dense plaque is formed in both contacting cells. At
the same time there is a slowing down of the amoeboid process which results in contact inhibition of
movement. In contrast, cancer cells are unable to form adhesive junctions and do not show this type
of contact inhibition.

Experimentally, it has been observed that when normal cells have become completely surrounded by
other cells, their mobility stops and they form a monolayer. At the same time there is inhibition of
growth and the number of cells in the petridish remains practically constant.

On the other hand, cancer cells continue to multiply and pile up forming irregular masses several
layers deep. Cancerous cells undergo a change in property of their cell membranes and cell coat such
as disappearance of gap junction, loss of coupling changes in glycolipid and glycoprotein and a
reduction in gangliosides.

In the cell coat fibronectin, a large glycoprotein found in footprints of moving cultured cells is
reduced in cancerous cells. These changes enable the cells to dissociate from neighbouring cells and
show loss of contact inhibition.

(iii) Reduced Cellular Adhesion:

Most cancer cells are less adhesive than the normal cells due to reduced expression of cell surface
adhesive molecules. When normal cells are transformed into cancer cells, then a change of stickiness
of their cell membrane results. Normal cells show stickiness or adhesiveness.

If normal cells are grown in a liquid nutrient medium kept in a glass vessel, the cells stick to glass wall
rather than float in the medium. But when cancer cells are allowed to grow in nutrient medium, they
stick to each other less than do normal cells.

Adhesiveness shows considerable specificity. For example, a liver cell tends to stick with another liver
cell and not to other types of cell such as kidney cell. Cancerous cells do not show this property. They
are able to mix and stick to any type of normal cell. For example, a malignant liver cell can mix and
stick to normal kidney cell. Hence this unusual behaviour of cancer cell explains that cancer cells can
invade several normal organs.

(iv) Invasiveness:

One of the most important characteristics of cancer cells is their invasiveness. It is the ability to
invade other tissues. Malignant cells generally secrete proteases that digest extracellular matrix
components, allowing the cancer cells to invade adjacent normal tissues. For example, secretion of
collagenase by the cancer cells helps to digest and penetrate through basal laminae to invade the
underlying connective tissue.

Cancer cells also secrete growth factors that promote the formation of new blood vessels. This is
known as angiogenesis. Angiogenesis is necessary to support the growth of tumour beyond the size
of about a million cells at which point new blood vessels are needed to supply oxygen and nutrients
to the multiplying tumour cells.

Actually the growth factor secreted by the tumour cells stimulates the endothelial cells present in
the wall of capillaries.
As a result, new outgrowth of the capillaries is formed into the tumour. These outgrowths of
capillaries are also helpful for metastasis of malignant cells. Therefore, angiogenic stimulation
induces the growth of new blood capillaries which penetrate easily in the tumour tissue and provide
the opportunity for the cancer cells to enter the circulatory system. As a result, metastasis process
begins.

(v) Failure to Differentiate:

Another general characteristic of most of the cancer cells is that they fail to differentiate. This
property is closely related with the abnormal proliferation. Normal cells are fully differentiated. In
most fully

differentiated cells, cell division ceases. In case of cancer-cells, normal differentiation program is
blocked at the early stages of differentiation. The relationship between defective differentiation and
rapid proliferation is clearly noted in case of leukemia.

All of the different types of blood cells develop from a common pluripotent stem cell in the bone
marrow. Some of the descended cells develop erythrocytes but others differentiate to form
lymphocytes, granulocytes and macrophages. Cells of each of these types become round as they
differentiate but once they become fully differentiated cell division ceases But leukemia cells fail to
undergo terminal differentiation. Instead, they become blocked at early stage of maturation at which
they retain their capacity for proliferation and continue to divide.

(vi) Auto stimulation of Cell Division:

Cancer cells produce growth factor that stimulates their own cell division. Such abnormal production
of a growth factor by the cancer cell leads to continuous auto stimulation of cell division. This is
known as autocrine growth stimulation. Hence the cancer cells are less dependent on general growth
factor produced within the body physiologically from normal source for inducing growth of all
normal cells. It is also noted that the reduced growth factor dependence of cancer cell results from
abnormalities in intracellular signalling system.

(vii) Apoptosis:

For every cell, there is a fixed span of life, i.e., time to live and time to die. This cell death is a very
orderly process and so it is called Programmed Cell Death or PCD or Apoptosis. Apoptosis is a
mechanism of programmed cell death or cell suicide which is essential for the survival of the
organism, for the normal development of the organism as the programmed destruction of the
organism as the programmed destruction of cells is found during embryo-genesis. It also protects the
organism by removing damaged cells which may be due to viral infection or due to exposure to
radiations. It also inhibits the tumour development and so any defect in the control of apoptosis may
lead to cancer.

There are two methods by which cells may die such as:

1. Death by injury that is through mechanical damage or due to toxic chemicals.

2. By Apoptosis, i.e., through programmed cell death.

(a) Characteristic charges during apoptosis:

The following distinct morphological changes are found during apoptosis:

1. Shrinkage of cells.

2. Cell forms tight sphere.

3. Cell membrane forms bubble-like blebs on the outer surface.

4. Occurrence of nuclear membrane break.

5. Breakage of cells into small fragments.

6. Engulfment of cells fragments by phagocytic cells:

(b) Genetic Control of Apoptosis:

Some apoptosis genes have already been identified which are responsible for switching on or off
apoptosis. These genes include ICE (Interleukin-lb-Converting Enzyme) and P53. There are other
factors that also regulate the process of apoptosis.

One of them is the signal protein which is released either due to some cell injury or through cytokine
medicated pathways. There are some critical proteins or modulating factors which determine
whether a cell will be repaired or undergo death.

These genes or factors may initiate some stimuli for cell death or induces cellular susceptibility to
apoptosis or initiates some effector mechanisms for apoptosis. Some of the genes or factors
responsible for apoptosis are listed in the Table 23.1.
(c) Mechanism of Apoptosis:

There are generally three different mechanisms for apoptosis. These are:

1. Triggered by internal signals, i.e., signals arising within the cell.

2. Triggered by external signals.

3. By Apoptosis-Inducing Factor (AIF).

1. By Internal Signals:

In a normal cell, the protein (BC1-2) produced from a gene BC1-2 remains on the outer surface of the
mitochondria. The protein BC1-2 holds the apoptotic protease activating factor- 1 (Apaf-1). But when
the damage occurs in the cell internally due to some reactive oxygen, the Apaf-1 factor is released
from BC1- 2-Apaf-l complex.

This allows the protein Bax to penetrate the mitochondrial membrane causing a leakage of
cytochrome C from the mitochondria.

Then the released cytochrome C and Apaf-1 bind to molecules of caspase 9. The complex containing
cytochrome C, Apaf- 1, caspase 9 and ATP is called Apoptosome. Caspase 9 is actually one form of
protease which cleaves proteins at Aspartic acid residues.

The caspase 9 activates other caspases creating a cascade of proteolytic activity which leads to the
lysis of cell through digestion of structural proteins of the cytoplasm and degradation of
chromosomal DNA.