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Colon cancer spread reversed in lab
Source: (cancerfacts.com)
Monday, January 05, 2004
REHOVOT, ISRAEL – Jan. 5, 2004 – Scientists have succeeded in laboratory experiments in reversing the ability of colon cancer cells to enter the blood stream and spread to other parts of the body.
The research team led by Dr. Avri Ben-Ze'ev of the Weizmann Institute of Science in Israel says the findings reveal a key process involved in spread or metastasis of colon cancer cells. They also raise hopes that drugs targeting the mechanism might be devised to prevent, or reverse, the invasive behavior colon cancer cells. The study was first published in the Nov. 24, 2003 issue of The Journal of Cell Biology.
"The fact that the invasive process in colon cancer can be reversed is surprising," says Ben-Ze'ev. "It offers hope of reversing the metastatic process or even preventing it in the future by designing a drug that targets Slug."
Cells are held together by adhesion molecules, including two key molecules called beta-catenin and E-cadherin, which are found near the surfaces of cells. Beta-catenin also has another function: when inside the nuclei of cells, it regulates the expression of genes. Beta-catenin is known to be involved in various cancers, including colon cancer, by aberrantly activating genes whose identity is mostly unclear. In previous research, Ben-Ze'ev's team identified several such genes that are involved in the progression of human melanoma and colon cancer.
Now, the scientists have found that when a colon cancer cell becomes metastatic, abnormally large amounts of beta-catenin are found in its nucleus and, unexpectedly, they bring about a reduction in adhesion. The cell can thus break loose from the tissue and migrate to form another tumor at a distant site.
Beta-catenin in the nucleus does this by activating a gene called Slug. Slug inhibits the production of beta-catenin's partner in cell adhesion, E-cadherin. The shortage of E-cadherin prevents the cell from adhering to adjacent cells. The cell takes on a boat-like shape and, leaving the pack, invades neighboring tissues until it enters the bloodstream. This migrating cancer cell can, in time, form a new tumor by entering distant tissue via the bloodstream and multiplying there.
Ben-Ze'ev's team discovered that, when such a colon cancer cell becomes surrounded by other such cells in a crowded environment (whether in the body or in the lab), minute quantities of E-cadherin in the cell recruit beta-catenin from the nucleus and can thus begin the process of binding together.
Lower levels of beta-catenin in the nucleus result in decreased Slug production (and increased E-cadherin production). As a result, the cells stick together and form a tissue-like organization – losing their metastatic properties. This is precisely the process that the scientists hope to be able to induce in patients to block metastasis.
Colon cancer is the second most prevalent type of cancer in men and third in women in the Western world.
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