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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

Mary is a 46-year-old mother of two daughters, ages 17 and 19. Eight years ago she was diagnosed with breast cancer, and after a conventional course of chemotherapy followed by radiation, the cancer was driven into remission. Lately she is having increasingly severe back pains. At a routine check-up, she mentions the pains to her surgeon, who performs a bone scan. The scan reveals several "hot spots," regions of increased metabolic activity in her spinal column. The diagnosis made on a biopsy of one of these hot spots catches her completely off guard: metastasis of her breast cancer.

Patients like Mary inevitably ask the question: Why me? But for those of us who study what cancer is, its development and spread, the question is rather: Why at all?

Figure 1. Before spreading to new organsClick to Enlarge Image

The simple answer is that in cancer the genes and chromosomes of cells become disorganized, leading them to enact genetic programs far different from the intended normal program. It has often been noted that cancer cells are unusual because they are undifferentiated; that is, they lose functions and, as a result, fail to fully develop the characteristics and proper activities of mature cells of their type. Quite remarkably, metastatic cancer cells gain new functions, taking on characteristics unrelated to the normal, often sedentary cell type.

Most cells are designed to remain fixed in their organs in order to perform the specialized activities for which they are particularly adapted. They are held tightly in place by molecular tethers that link them with the other cells and the proteinaceous matrix in that tissue. Clearly, these cells are not meant to roam around the body and take up residence in other organs. Metastatic cancer cells are altered in such a way that they can break those bonds. Further cellular remodeling allows metastatic cells to chew through the proteinaceous walls that line tissues and blood vessels and quite literally walk away from their parent organ to invade other tissues and organs.

If it were not so potentially damaging, metastasis might be just an interesting cellular oddity. But the fact is that the metastatic tumor is often more dangerous than the original, or primary, tumor. Metastatic cancer cells crowd out normal cells in the tissue and deprive them of nutrients. In effect, the metastatic cells starve and displace functional cells. This can be lethal when the organ—or organs, since cancer cells can go almost anywhere and often end up in several new organs—can no longer perform its vital functions.

Over the past few decades, biologists have become ever more precise in determining the genetic, biochemical and cellular changes that drive a cell first to become cancerous and then to become metastatic. And new discoveries are being reported daily. So, although not all of the details are entirely known, a comprehensive picture of these alterations is emerging. Each new piece of information not only contributes to this overall picture; it also provides a site of potential therapeutic intervention to inhibit the progression of cancer—if not, someday, to eliminate it entirely.

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