Differing Immune Systems' Effects on Cancer Rates

Differing Immune Systems' Effects on Cancer Rates

Abstract

This scope of this research proposal is large, as it encompasses two different species' immune systems and the effects of those immune systems on cancer rates. The overall focus of this research will be on why and how sharks have a lower cancer rate than humans do. This will require comparing a shark immune system to a human child immune system and a human adult immune system. Although these two systems are similar, there are some very important differences between the two. We will also be doing in depth research on the epigonal organ of the shark and its possible function of producing T-cells and blood cells that make up its immune system. Finally, we will be investigating if the shark immune system is resistant to autoimmune and immunoresistant diseases, as well.

Introduction

Human Adult Immune System

The immune system is a way of protecting the body against infection. A part of the immune system is the white blood cells, called neutrophils. Neutrophils find and kill bacteria and other infectious agents (Cancer Research UK 2002). An adult human's normal neutrophil count is between 3,000 and 6,000 neutrophils per millilitre of blood (Cancer Research UK 2002). When people have a low neutrophil count, infections can spread more easily. Another part of the immune system is T-cells. One type of T-cells is killer T-cells. Killer T-cells attack the cells of the body that have already been infected. The other type of T-cells is helper T-cells. Helper T-cells stimulate the B-cells to make antibodies. B-cells create antibodies as a reaction against invading bacteria or viruses. Antibodies are proteins with two ends. One end, named the constant end, is attached to the white blood cell. The other end, named the variable end, recognizes germs and damaged cells. There are B-cells that recognize cancer cells and will try to stick to them (Cancer Research UK 2002).

Human Infant & Shark Immune System

Human infants and sharks seem to possess only one class of broad-spectrum serum antibody. As the human infant grows, more specific antibodies replace this broad-spectrum serum antibody. However, sharks retain their non-specific immune response their entire life. This non-specific immune system allows sharks to detoxify many harmful compounds quickly, without prior exposure (Martin 2000).

Development of Cancer

It is very unlikely for the human immune system to prevent or "cure" cancer. The cause of cancer is not extensively known. However, studies have observed the similarities between cancer cells and oocyte cells. An oocyte or ovocyte is a female gametocyte (Wikipedia 2006). Studying oocyte cells could lead to understanding how cancer is caused (Majerus MA 2002).

Sharks & Cancer

It has been observed that sharks have a very low rate of developing cancer. A large area of research has been dedicated to shark cartilage and its prevention of cancer. However, we would like to look at other causes of the low rate of cancer in sharks. The role of immune regulatory molecules on inhibition of the growth of tumor cells has been another area of research (Self 2005). Certain molecules, secreted by shark cells, are introduced to cancer lines on a culture. The results have shown that 80% of the cancer cells die. Something in the shark's cells is preventing and destroying the cancer. Also, sharks that have been injected with carcinogens have been able to detoxify the pathogen and survive, without ill effects (Martin 2000).

Epigonal Organ

In sharks, there is a pair of organs underneath the kidneys, called the epigonal organ. There is very little information on where this organ comes from, or what it does. Research has shown that the epigonal organ contains lymphoidal tissue and may have a blood cell-forming function. The epigonal organ plays a large role in the shark's immune system, since research has shown that it is the site of T-cell differentiation.

Research Goals

(1) Determine the effect of the compound, squalamine, on tumor growth.

(2) Determine the rate of cancer in clearnose skates after exposure to carcinogens.

(3) Determine the function and importance of the epigonal organ.

Materials and Methods

Effect of Squalamine on Tumor Growth

Blood is transported throughout the body through a network of arteries, capillaries and veins, known as the vasculature. The basic network of the vasculature is developed through angiogenesis, a process by which new blood vessels are formed. This embryonic vasculature is primarily developed through the first three months of fetal development. Once the general network of the blood vessels is completely developed, the balance of certain stimulatory and inhibitory factors stabilize new blood vessel formation associated with wound healing and reproduction.

A tumor can be thought of as an uncontrolled cellular growth. Like all cells, tumors need nutrients and to eliminate waste products (Salvatore 1998). To accomplish this, tumors secrete the angiogenin hormone, which causes nearby blood vessels to grow new branches that surround it. It is believed that an anti-angiogenic compound found in dog sharks, called squalamine, can kill tumors or, at least, slow tumor growth. Squalamine is the first known example of a class of compounds called aminosterols, a steroid chemically linked to an amino acid (Mack 2004).

Preliminary research has shown that "squalamine appears to act early in the chemical cascade that controls angiogenesis, when cells begin to proliferate and migrate. The tumor's stimulatory signal reaches a receptor on blood vessel cells, which, in turn, is relayed through several cellular proteins before cell division accelerates" (Mack 2004). Other compounds guide the vessels' growth toward the tumor and their subsequent infiltration of the mass.

In order to test the anti-angiogenic capabilities of squalamine, a tumor will be implanted into the cornea of a rabbit. This corneal tissue will then be treated with squalamine to determine whether it will block the formation of new blood vessels, thus starving the tumor. Corneal tissue is normally bloodless, so if blood vessels begin to form