What happens when development goes wrong?
This leads to the development of cancer and abnormal development.
Characteristics of cancer;
This is abnormal development and the cells are dividing when they should not.
Cancer can occur in virtually any cell type. However, it is more frequent in some cell types than
Within a cancer, patients can show variations in the symptoms.
There is a loss of control of cell division. These are cells that are dividing when they should
There is also invasiveness. This is when they are migrating to other tissues when they should
The cover slide shows cancer cells growing in tissue culture. On the bottom of the dish they are
sending out trails that are invading into other cells.
What is the mechanism that tells a normal cell to start dividing and when to stop dividing?
Studies were needed to determine what goes wrong in cancer cells.
To understand we needed to understand what happens in a normal cell in relation to division.
A normal cell is undergoing a controlled rate of cell division. A cancer cell is undergoing
uncontrolled division and it is dividing in places within the body where it shouldn’t.
This is a normal cell transforming into a cancer cell.
There is a loss of normal cell division control.
States of Cancer:
There are two (2) formats;
All cancer cells remain together in a mass. This mass of cells forms a clump of cancer cells in
one location. The cells at the center are the original cells and the newer cells are on the outside.
The cells at the center are usually dead as they cannot get nutrients.
This type of cancer is usually removed by surgery. If there are any remaining cells left after
surgery, the tumor will re-grow.
Sometimes a tumor is just a stage. Sometimes they will leave the original tumor site and invade
other cells. An example is breast cancer. The tumor metastasizes into another area of the body.
There is a spread of cancer. When the cancer is in the tumor form it can be removed. However
when it’s metastasizing it is more difficult to treat and chemotherapy and/or radiation must be
1 What types of cells become cancerous?
Any type of cell can transform into a cancer.
There are cells in the body that are dividing in a controlled way, sometimes these cells change
from controlled to uncontrolled.
Neurons that do not divide can also transform and begin to divide.
Normal cells vs. cancer cells:
What goes wrong in the cancer transformation?
We could compare phenomenon within the cells that are normal and cells that are cancerous.
Principal of contact inhibition:
It is lost in cancer cells.
Normal cell adhesion:
Adhesion properties change in cancer cells.
Cell recognition changes in cancer cells.
Principal of contact inhibition:
There are two (2) rules;
Normal cells exhibit contact inhibition as shown by;
1) when normal cells touch each other they stop moving
2) they develop a signal that stops further cell division
How can we study these rules?
We can grow normal cells in tissue culture.
In the diploid state the cell likes to sit on the surface.
When dividing (4n) and cell rounds up, comes off the glass and divides into two (2) then settles
on the surface of the dish again. This continues until a single layer of cells fills the bottom of the
dish. When the dish is filled, they are touching each other and they stop moving and they stop
This is the Principal of contact inhibition.
The monolayer controls the division, when they touch they generate a signal and they stop
moving and stop dividing.
In a cancer cell, 2n goes to 4n, they divide and continue. However, cancer cells continue after
the monolayer is complete. They continue to divide even though the layer is full. They have lost
the ability to stop dividing. They have lost the property of contact inhibition.
When cells touch each other they stop moving then stop dividing. This suggests some form of
cell recognition. The piling up of the cancer cell suggests that something has happened with the
2 Normal cells;
Experiments on cell adhesion and cell recognition;
They took normal liver cells and minced them into small pieces. They were then put into a
medium with no Ca+ or Mg+ ions. These ions are required for adhesion recognition. This
allows them to recognize other liver cells. When in a medium with no Ca+ or Mg+, the cells
dissociate into single cells that have no cell surface adhesion recognition. Cells are making
adhesion proteins but they cannot stick. When we add Ca+ and Mg+ they are able to adhere
together because they now recognize each other.
If we mix two (2) types of cells;
Liver and kidney adhesion proteins are made, but they do not stick together. When ions are
added, they can stick and they now find each other and begin to clump together. Cells have
sorted themselves out and can recognize similar cell types.
Cell Adhesion, cancer cells:
If we mix normal kidney cells with malignant skin cells from a tumor, strip off the cell
recognition proteins and add Ca+ and Mg+. The two (2) cells do not sort themselves out, but
clump all together with the cancer cells and the kidney cells. The cancer cells have something
wrong with the recognition proteins.
During transformation the cells lose the contact inhibition property, but something has changed
in the cell recognition. They have however, obtained the property of invasiveness.
Another way is to compare the biochemistry of a normal cell and the cancer cell that resulted
from the transformation of the normal cell.
Comparison of proteins in normal and cancer cells:
If we saw the differences could we see what happens?
When a new protein is discovered the normal and cancer cells are evaluated and they see if the
enzyme has changed. If the protein has gone up or down, could this be an indication of cancer
This is the protein profile comparison.
Problems of this comparison;
If there is a change we don’t know if this is a primary or secondary effect. Some is from the
basic principal of differentiation. Secondary may have been from the chemical that was used.
How do we know the cancer was caused from the primary or secondary?
Sometimes, it is difficult to tell the normal cell that the cancer cell arose from. This is because
during transformation the cell undergoes dedifferentiation. If from a neuron, the cancer cell
loses some of its neuronal properties. They lose their original properties from the normal cell.
We then don’t know what cell the cancer came from.
This is a biochemical principal that cancer cells produce an abundance of lactic acid. This is
called the Warburg effect.
3 Most tumors rely on anaerobic glycolysis to live in low oxygen environments. This causes them
to use a lot of glucose. This is a feature of tumor cells. This benefits the growth condition of the
cancer cell and allows them to out compete normal cells. There is a decrease in the pH in the
Lactic acid comes from glucose. Glycogen is a source material for glucose which comes from
the liver. Glycogen is broken down to produce glucose. Tumor cells take it up and the waste
product of this breakdown is lactic acid.
Antigenic differences between normal and cancer cells?
We know the body’s immune system is designed to detect and destroy foreign substances. There
are antigens in the cells and they make antibodies. These antibodies attack and destroy the
It was thought that it is unlikely cancer cells would show different antigens from normal cells. If
they did the body’s immune system would detect and destroy those cells.
The current belief is that cancer cells do show antigenic differences. This happened through
research on organ transplantation. To avoid rejection, the patient is giving immunosuppressant
drugs. The new organ is rejected because the body knows it is not it’s own. The drugs are given
to suppress the immune system and reduces the probability the organ will be rejected.
There was a side effect and some patients showed higher than normal incidences of cancer.
It was then thought if you suppress the immune system, cancer may be able to happen more
Cancer may be caught and eliminated by the body by IMMUNOSURVEILLANCE. The body is
constantly scanning the body for cancer and body can eliminate these cancer cells.
The immune system is then catching the proteins on the cancer and is destroying them. When
we suppress the immune system the body can’t work in this way and cancer occurs. People with
defective immune systems have a higher chance of cancer.
During cancer transformations new proteins are produced and the body detects them.
Why do some cancers not get detected?
The body may be fooled by the cancer by antigens that resemble fetal antigens. The body
remembers these antigens and allows the cancer to continue.
Can immunosurveillance be used to attack the cancer that normally escapes detection?
Staging of cancer malignancy:
Cancer development states with initiation, this is the mutation of a single cell.
Promotion is when the single cell divides to produce many cells that have the mutation.
Progression is the addition of another mutation and the cell becomes malignant.
What are some of the things that can cause a normal cell to become a cancer cell?
4 There are three (3) different agents that we will talk about.
These are chemicals that can have a strong ability to change normal cells to cancer cells. Some
are more powerful than others. Examples can be asbestos which is a fiberous material that is
harvested by pounding of rock. These fibers can be removed from the rock. It is very good to
protect against fire and heat. It was used as insulation in building houses and business. 20-30
years ago we began to see the workers who were using this substance were coming down with a
lung cancer (malignant mesothelioma) which was specific to certain cells. The fibers were
breathed into the lungs and these fibers were triggering cancer transformation in the lung cell.
Asbestos needs to be remo