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Mobile cancer stem cells can form metastases in colon cancer and other malignant tumours. Professor Thomas Brabletz from the University Hospital Freiburg, Germany, has developed a new model, which he presented at the International Conference "Invasion and Metastasis" held at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin. "Therefore, mobile cancer stem cells are the most dangerous cells for cancer patients," he said. Until recently researchers assumed that every single tumour cell could form metastases.
According to the World Health Organization, 655,000 people die from colon cancer every year. After lung cancer, it is the second most common cause of cancer-related deaths. This type of cancer arises from glands of the colon mucosa. It often goes unnoticed during the initial stage of development. Indeed, affected patients rarely present with pain or other symptoms, and thus the cancer is often not spotted until dangerous metastases have already developed.
Cancer stem cells in colon cancer develop from colon stem cells, Professor Brabletz stated. These stem cells normally ensure that colon cells, which have a very short life span, are replaced each day. When such a stem cell becomes a cancer stem cell, it can divide infinitely and produce more cancer stem cells. In the second step of development, the altered cell detaches from the primary tumour and is then able to disseminate through blood or lymphatic vessels in the body.
"The specialized cancer stem cells activate pathways," Prof. Brabletz explained, "that the body has used during its embryonic development and which have since been silent." The erroneously activated pathways liberate the original stem cell from signals in its environment. Normally these signals strictly control the activities of every single stem cell.
"However, these stationary, immobile cancer stem cells are not yet able to form metastases," Prof. Brabletz pointed out. Again, changes in important pathways of the cell or its environment play a crucial role in this process. That is, a cancer stem cell is able to further change its characteristics and thus lose contact to its neighbours: It has then become mobile. This process is known as epithelial-mesenchymal transition (EMT). At that point, the mobile cancer stem cell can enter the bloodstream and reach regions in the body which are far away from the original tumour. When it encounters a new, suitable environment, it can settle down and form a metastasis. In the case of colon carcinoma, metastases preferentially colonize the liver.
With this model of mobile cancer stem cells, Professor Brabletz is certain that for the first time he and his colleagues have joined all current theories on metastasis formation - genetic aberrations, changes in the tumour environment, cancer stem cells and EMT. In his view, it is not possible to understand the formation of metastases by looking solely at one concept- for example the concept of cancer stem cells.
He pointed out that the crucial steps for metastasis are reversible. "This cannot be explained by irreparably altered genes", he insisted. Once a mobile cancer stem cell has arrived at its destination, which in the case of colon cancer is the liver, it is transformed into a stationary cancer stem cell again. The transformation program is shut down. "There has to be a component which is able to cause the transformation of these cells in one or the other direction," he said. We still don't know what this component is. However, Prof. Brabletz thinks that growth factors from the tumour environment might be responsible for converting a stationary cancer stem cell into a mobile cancer stem cell.
Should the new model of metastasis formation be verified in the course of the next few years, Prof. Brabletz is convinced that there would be serious consequences for fundamental and clinical research,. "Mobile cancer stem cells would be ideal targets for cancer therapy," he believes. "They are the most dangerous cells for cancer patients because, according to our model, they are the main origin of metastases."
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
http://www.mdc-berlin.de/en/news
http://www.uniklinik-freiburg.de/brabletz-lab/live/prof_en.html
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