1 Colon cancer becomes fatal as soon as the cancer spreads to other organs in the body, especially the liver. Researchers from the Weizmann Institute discovered a gene that controls the rate of spread of metastases
The expression of certain genes - which drive the spread of cancerous tumors in the early stages of the disease - is later inhibited. This is an action necessary for the continued progression of the cancer. Prof. Avri Ben-Zev, from the Department of Molecular Cell Biology at the Weizmann Institute of Science, showed that in the late stages of colon cancer, the cancerous tumor cells take a big step back, so that some of their gene expression patterns are distinctly similar to those of healthy stem cells in the intestines.
Colon cancer becomes fatal as soon as the cancer spreads to other organs in the body, especially the liver. Prof. Ben-Zev and members of his group previously discovered a mutation, found in 80% of this cancer, which leads to increased expression of a gene called L1 - especially in cells that are at the forefront of the spread of metastases. The current study, which began due to the desire to understand the meaning of this gene expression, led the research group to delve into another gene - called SMOC-2 - which has far-reaching effects on the spread of liver metastases.
The scientists studied in model mice the role of this gene in the process of creating metastases of colon cancer in the liver. They found that L1 causes increased expression of the SMOC-2 gene in the cells that form the metastases. Next, they artificially increased the level of SMOC-2 in human-derived colon cancer cells. As a result, the activity leading to the development of metastases increased. On the other hand, inhibition of this gene inhibited the formation of metastases.
But what is the function of this gene? SMOC-2 codes for a protein that the cells secrete, and it helps increased cell movement. This molecule, apparently, helps differentiating stem cells to detach from their neighbors at the bottom of the "coils" of the intestine, and move up towards the intestinal cavity. In addition, it seems that by activating SMOC-2 in colon cancer cells, the cells can "leave the house", and the necessary cellular movement to form metastases is possible. "This study", says Prof. Ben-Zev, "supports the idea that it is possible that as the cancer develops, some of its cells adopt a pattern of gene expression similar to that of stem cells from the intestine." Another study carried out in Prof. Ben-Zev's laboratory, which focused on the interrelationships between SMOC-2 and other genes, showed that metastatic cancer cells from the human intestine did adopt several properties of normal stem cells of the intestine.
Prof. Ben-Zev hopes that future research will indicate possible ways to interfere with the activity of genes such as SMOC-2, and to curb the process of spreading metastases. "In addition," he says, "the expression patterns of SMOC-2 may be used as an effective and reliable marker for the early detection of colon cancer metastases in humans."
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