Jul 26, 2012

Loss of Cell Cycle Controls in Cancer Cells

Cancer cells do not respond normally to the body’s control mechanisms. They divide excessively and invade other tissues. If unchecked, they can kill the organism.

By studying cells growing in culture, researchers have learned that cancer cells do not heed the normal signals that regulate the cell cycle. For example, as the figure above shows, cancer cells do not exhibit density–dependent inhibition when growing in culture; they do not stop dividing when growth factors are depleted. A logical hypothesis to explain this behavior is that cancer cells do not need growth factors in their culture medium in order to grow and divide. They may make a required growth factor themselves, or they may have an abnormality in the signaling pathway that conveys the growth factor’s signal to the cell cycle control system even in the absence of that factor. Another possibility is an abnormal cell cycle control system.

There are other important differences between normal cells and cancer cells that reflect derangements of the cell cycle. If and when they stop dividing, cancer cells do so at random points in the cycle, rather than at the normal checkpoints. Moreover, in culture, cancer cells can go on dividing indefinitely if they are given a continual supply of nutrients; they are said to be “immortal.” A striking example is a cell line that has been reproducing in culture since 1951. Cells of this line are called HeLa cells because their original source was a tumor removed from a woman named Henrietta Lacks. By contrast, nearly all normal mammalian cells growing in culture divide only about 20 to 50 times before they stop dividing, age, and die.

The abnormal behaviour of cancer cells can be catastrophic when it occurs in the body. The problem begins when a single cell in a tissue undergoes transformation , the process that converts a normal cell to a cancer cell. The body’s immune system normally recognises a transformed cell as an insurgent and destroys it. However, if the cell evades destruction, it may proliferate and form a tumour, a mass of abnormal cells within otherwise normal tissue. If the abnormal cells remain at the original site, the lump is called a benign tumour . Most benign tumors do not cause serious problems and can be completely removed by surgery. In contrast, a malignant tumour becomes invasive enough to impair the functions of one or more organs.
An individual with a malignant tumour is said to have cancer.

The cells of malignant tumours are abnormal in many ways besides their excessive proliferation. They may have unusual numbers of chromosomes (whether this is a cause or an effect of transformation is a current topic of debate). Their metabolism may be disabled, and they may cease to function in any constructive way. Also, owing to abnormal changes on the cells’ surfaces, they lose or destroy their attachments to neighbouring cells and the extracellular matrix and can spread into nearby tissues. Cancer cells may also secrete signal molecules that cause blood vessels to grow toward the tumour. A few tumour cells may separate from the original tumour, enter blood vessels and lymph vessels, and travel to other parts of the body. There, they may proliferate and form a new tumour. This spread of cancer cells to locations distant from their original site is called metastasis.

A tumour that appears to be localised may be treated with high–energy radiation, which damages DNA in cancer cells much more than it does in normal cells, apparently because cancer cells have lost the ability to repair such damage. To treat known or suspected metastatic tumours, chemotherapy is used, in which drugs that are toxic to actively dividing cells are administered through the circulatory system. As you might expect, chemotherapeutic drugs interfere with specific steps in the cell cycle. For example, the drug Taxol freezes the mitotic spindle by preventing microtubule depolymerisation, which stops actively dividing cells from proceeding past metaphase. The side effects of chemotherapy are due to the drugs’ effects on normal cells. For example, nausea results from chemotherapy’s effects on intestinal cells, hair loss from effects on hair follicle cells, and susceptibility to infection from effects on immune system cells.

Researchers are beginning to understand how a normal cell is transformed into a cancer cell. Though the causes of cancer are diverse, cellular transformation always involves the alteration of genes that somehow influence the cell cycle control system. Our knowledge of how changes in the genome lead to the various abnormalities of cancer cells remains rudimentary, however.

Perhaps the reason we have so many unanswered questions about cancer cells is that there is still so much to learn about how normal cells function. The cell, life’s basic unit of structure and function, holds enough secrets to engage researchers well into the future.