Friday, January 15, 2010

What Causes Cancer

What causes cancer? We all know that cancer cells are different from normal cells. One of the hallmarks of cancer cells is that they lose control over cell reproduction. Normally, cells control when and where they reproduce. They do it in two ways. There are internal controls. Normally, there is an internal clock inside a cell that triggers in the cell division cycle.

Most mature(specialized) cells do not divide. Immature cells divide rapidly (think of an embryo or bone marrow). What keeps cells dividing is a group of proteins that stimulate them. What keeps them from dividing is a set of proteins that blocks them from cell division. Because they block tumors from forming, we call them tumor suppressors. These proteins act the control points during cell division.

Cancer cells have defective tumor suppressors. They have mutations in their DNA that causes the protein that normally functions to block cell division to not function. Those are the internal controls of cell division.

There are also external controls in cell division. The external controls are hormone-like substances called growth factors. They stimulate cells to divide by acting like a gas pedal in a car. For example, a blood clot forms and then the wound heals, so the skin around the blood clot heals, and the clot goes away. The cells that surround the blood clot have to be stimulated to do so. Those cells have to surround the blood clot and close the wound. “Closing the wound” is not a biological term, what really happens is a lot of cell division. In turns out that the same cells that form the clot stimulate the cells above it to heal. The clot makes a growth factor that stimulates the skin cells to divide, reproduce and heal the wound.

Genes whose protein products stimulate cell division in this way are called oncogene. Cancer cells usually make their own growth factor. They would have an oncogene that is mutated, so it is producing constant stimulation for cell division. Other cancer cells may have genetic changes that make them hypersensitive to even tiny amounts of growth factors. These are the genes that turn on the gas pedal of cell reproduction.

The most fearsome aspect of cancer is that cancer cells can spread to other organs. This is called metastasis. You can’t do surgery if a tumor is all over the place. This leads to multiple organ failures, and it is really what often causes people to die of cancer.

Normal cells have a “glue” that causes the cells to stick to one another. This glue is specific. If you pinch your skin, you will notice that the cells at the skin stick together and are separate from the bone. They must have a specific “glue”, which is formed by proteins. There are cell recognition and adhesion proteins. Cancer cells loose this adhesion.

There are several steps in metastasis. First, cancer cells have to loose their adhesion and detach from the tumor. Then, the cells make it to the bloodstream or lymph system. In the blood, they travel to an organ. They stop at the new organ and grow as a satellite tumor. We know all of these steps in great detail at this point.

This events: inactivation of tumor suppressors, activation of oncogenes and metastasis; occur in sequence. Cancer is a multi-step disease. To be continued…

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