Understanding and Controlling Metastasis
The main cause of treatment failure and death in cancer patients is metastasis, the spread of the tumor from a primary site to new tumors in distant organs. Given its importance, therefore, it behooves researchers to devise treatment methods that specifically target the metastatic process. Until recently, however, the field was hindered by an incomplete understanding of the metastatic process.
The metastatic process
As the primary tumor grows, it is developing a blood supply to support its needs, a process called angiogenesis. Without angiogenesis, a tumor would only grow to a limited microscopic size, enter into dormancy or die. Recently, it has been discovered that a parallel process known as lymphangiogenesis, or growth of lymphatic vessels, also occurs. 4
As the tumor cells multiply, the inherent genetic instability of cancer cells results in some cells acquiring the altered cellular properties necessary to metastasize. 1 The first step in the process is the metastatic cancer cell separating from its neighboring cells. This may take place due to defects in a structure known as cadherin, which binds cells together. Once released, the metastatic cells must pass through the extracellular matrix that surrounds the cells. The cancer cell accomplishes this by secreting enzymes such as matrix metalloproteinase, which breaks down the matrix.
The migrating metastatic cells encounter another barrier, the endothelial lining of the blood vessels. Other secretions allow the cells to pass through the lining and enter the blood. The cells have now left the tumor and entered into the body's circulatory system. The cells could also enter the system indirectly via the lymphatic system. The cells must survive in the circulation until they come to rest in a new organ. The cells become attached to the blood vessel lining with the help of adhesion molecules known as integrins. The characteristics of the metastatic cell determines the signals that it responds to, which in turn influences the tissue or organ that it ultimately establishes a new colony .The cancer cells leave the blood vessel by a process called extravasation into the surrounding tissue of the organ. In the new site, the cells may remain dormant for some time, or may be immediately stimulated to grow aggressively.
Why do certain cancer types show organ-specific patterns of metastasis?
In 1889, Stephen Paget proposed a "seed" and "soil" analogy to explain why various types of cancer form metastases in specific organs. In this analogy the cancer "seeds" are carried in all directions via the circulatory system, but can only live and grow if they fall on congenial "soil" (the secondary organ).
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