FEATURE ARTICLE
Metastasis
The spread of cancer cells to distant sites implies a complex series of cellular abnormalities caused, in part, by genetic aberrations
Cornelis J. Van Noorden, Linda Meade-Tollin, Fred Bosman
Regulating Proliferation
As with all cellular functions, a cell's life and death are under strict genetic control. These genes encode proteins that sense growth signals from the environment, or drive the cell through its replicative cycle and check for cellular and genetic abnormalities. Some of these regulatory proteins make the necessary corrections to damaged genes. Other proteins direct the cell to exit the cell cycle in order to differentiate. Still other proteins remove old or defective cells from the replicative cycle and send them en route to apoptosis.
It stands to reason that if any of these genes or the proteins they encode become faulty, the cell-division cycle will become abnormal. For example, alterations to the series of proteins that detects external growth cues can lead to an abnormally prolonged growth cue. Problems with the proteins that regulate the cell cycle can, likewise, maintain cells in a proliferative mode when they normally would exit the cycle and start to differentiate and mature.
In recent years, scientists have found that in the majority of cancer cells, one or several of these growth-regulatory genes is either missing or defective. It should be noted that all of these genes, when functioning properly, are crucial in maintaining the normal growth characteristics for each cell type. These genes only promote cancer when they become mutated or altered.
Cells on their way to becoming cancerous accumulate a number of genetic and chromosomal abnormalities, each of which in some way pushes the cell further in the direction of unrestricted growth. At first, clusters of genetically identical cells are formed, each cell dividing with less restraint than its normal neighbors. This cluster does not at this point constitute a tumor.
When the cell mass attains a diameter of about 2 millimeters, the cells emit signals that recruit surrounding connective tissue and vascular cells to the tumor and induce them to grow into blood vessels. The cell mass literally stimulates the growth of its own blood supply from existing blood vessels, a process called angiogenesis. There is some evidence that angiogenesis is probably initiated because cells in the mass, especially those in the interior, become starved for oxygen. In any event, once the blood supply is in place, the cell mass can import oxygen and the nutrients it needs to keep growing. Furthermore, the cells now have a conduit through which they can escape and invade other tissues. Angiogenesis seems to have an additional consequence. Connective tissue surrounding blood vessels release factors (as do the vascular cells) that stimulate the growth and motility of cancer cells. Strange as this may sound, cancer can only develop if the cancer cells are adequately supported by host tissues.
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