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Lecture 11

Lecture 11

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University of Toronto Scarborough
Biological Sciences
Ian Brown

LECTURE 11 What happens when development goes wrong? This leads to the development of cancer and abnormal development. Cancer: 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 others. 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 not. There is also invasiveness. This is when they are migrating to other tissues when they should not. 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. Transformation: 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; Tumor Invasive Tumor: 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. Invasive: 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 used. 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 dividing. 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 cell recognition. Cell Adhesion: 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 induction. 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. Warburg Effect: This is a biochemical principal that cancer cells produce an abundance of lactic acid. This is called the Warburg effect. Why? 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 cell. Anaerobic Glycolysis: 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 foreign antigens. 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 frequently. 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. Inducing Agents: 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. 1) Carcinogens 2) Radiation 3) Viruses Carcinogens: 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
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