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Hallmark of Cancer: Metastasis

The spread of cancer from its original location to other parts of the body is called metastasis. This is a critical event in cancer. About 90% of the death associated with cancer is due to disease that has spread. On this page, we present an introduction to the steps in metastasis of a cancer cell. Because of its importance, we have also created a section on how cancer spreads.

Into the Blood
Intravasion, or the process of gaining entry into the blood circulation, is the first step in metastasis. (1) To accomplish this, individual cells must move away from the primary tumor, which occurs through a change in adhesion molecules present on the cell surface. Adhesion molecules normally ensure that cells remain closely linked to each other and the basement membrane. However, in some tumor cells these molecules are no longer present allowing the cell to move away from the tumor and enter the blood stream. Normally, loss of adhesion molecules results in their death, this is a protective mechanism that helps prevent metastasis. Metastatic cells have developed mutations that allow them to disable this mechanism and survive in the absence of adhesion. (2)(3)

In the Blood
Once tumor cells have successfully entered the blood they face an entirely new challenge: surviving transit in the blood. Most cells, including tumor cells, are not designed to survive the stresses of the blood system. One of the primary ways in which tumor cells survive this transit is by co-opting platelets to act as shields. Platelets surround the cancer cells and protect them from both the force of blood flow and attacks from immune cells. (1)

Out of the Blood
Extravasation, or exit from the blood vessel, is the final leg of the tumor cell's journey through the circulatory system. In some cases, tumor cells, which are often larger than blood cells, get stuck in the capillary bed of a distant organ. Here they can continue to grow until they burst through the capillary wall. In other cases extravasion is more specific. Tumor cells are often drawn to certain organs based on compatibility of adhesion molecules present on the surface of the tumor cell and on the vessel wall. Capillaries in different organs have different sets of adhesion molecules and so metastatic cells may preferentially lodge in the capillary bed of specific organs (3). Evidence for this is observed in breast cancer, which frequently metastasizes to the lung. Breast cancer cells are capable of interacting with an adhesion molecule specifically present on cells of the lung (see section below on Organ Targeting).(4)

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Last Modified: 10/03/2011 Print Email Page
References for this page:
  1. Gupta, G.P., and J. Massague. 2006. Cancer metastasis: building a framework. Cell. 127:679-95. [PUBMED]
  2. Bacac, M., and I. Stamenkovic. 2008. Metastatic cancer cell. Annu Rev Pathol. 3:221-47. [PUBMED]
  3. Steeg, P.S. 2006. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 12:895-904. [PUBMED]
  4. Brown, D.M., and E. Ruoslahti. 2004. Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell. 5:365-74. [PUBMED]
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