metastasis Introduction Most cells of the body normally remain resident within a particular tissue or organ (though hematopoietic stem cells are a notable exception). Liver cells remain in the liver and cannot be found in the lung and vice versa. Organs have well-demarcated boundaries defi ned by surrounding basement membranes. Basement membranes are acellular structures made up of a fabric of extracellular matrix (ECM) proteins: predominantly laminins, type IV collagen, and proteoglycans. Cancer is distinctly characterized by the spreading of tumor cells throughout the body. The process by which tumor cells from a primary site invade and migrate to other parts of the body is called metastasis. Metastasis is the fundamental difference between a benign and malignant growth and represents the major clinical problem of cancer. A primary tumor can be surgically removed relatively easily, whereas once hundreds or more metastases have been established throughout the body they are practically impossible to remove. Sadly, many solid tumors have metastasized at the time of diagnosis. The spread of cells throughout the body results in physical obstruction, competition with normal cells for nutrients and oxygen, and invasion and interference with organ function. Interestingly, specifi c cancers metastasize to particular sites. Many of the preferences observed for the spread of specifi c cancers to specifi c metastatic locations can be explained by the directionality of blood fl ow. As the bloodstream is the predominant means of longdistance transport, organs in close proximity “en route” are likely to be main sites of metastasis for a particular primary tumor. However, about one-third of the locations of frequent metastases is puzzling in this regard. For example, a particular kidney cancer often metastasizes to the thyroid, a relationship that cannot be explained simply by anatomy. One explanation of this observation was described over 100 years ago in the “seed and soil” theory proposed by Stephen Paget. It described cancer cells as “seeds” requiring a match with optimal environments or “soils” to succeed. The ability of cancer cells to metastasize is dependent on the interactions of their cell surface molecules with the microenvironment, including neighboring cells and the extracellular matrix. Recent molecular evidence suggest that receptors lining the capillaries in the organs to which cancer spreads infl uence the destination of metastasized cells, and these fi ndings support the “seed and soil” theory. This theory is also supported by the concept of the establishment of a pre-metastatic niche, a site of future metastasis that is altered in preparation for the arrival of tumor cells. Further studies are needed to discover the factors needed for a tumor cell to be successful in metastasis. Although cancers are largely successful in metastasizing in the long run, on the cellular level, only 1 in 10,000 metastasizing cells survives transport.
Posted on: Tue, 30 Dec 2014 15:53:32 +0000