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The key process behind the metastasis of colon cancer is discovered by Catalan scientists

Scientists from the Colorectal Cancer Laboratory at the Barcelona Institute of Biomedical Research (IRB) have discovered the essential process that allows colon cancer cells to metastasise. They have concluded that tumour cells need to form alliances with healthy cells in order to be able to colonise other organs. Tumour cells can survive in the transition period during the metastasis process thanks to a protein (interleukin-11), which is produced by healthy cells that are exposed to another protein (TGF-beta) present in the tumour’s microenvironment. This discovery may lead to new treatments and diagnostic proceedings for colon cancer patients. A test to predict relapse cases and target treatments is likely to be ready in 5 years. The study has been published by the prestigious journal Cancer Cell.

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12 November 2012 11:25 PM

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ACN

Barcelona (ACN).- Scientists from the Colorectal Cancer Laboratory at the Barcelona Institute of Biomedical Research (IRB) have discovered the essential process that allows colon cancer cells to metastasise. According to a note released by the IRB on Monday, they have concluded that tumour cells need to form alliances with healthy cells in order to be able to colonise other organs. Tumour cells can survive in the transition period during the metastasis process thanks to a protein (interleukin-11), which is produced by healthy cells that are exposed to another protein (TGF-beta) present in the tumour\u2019s microenvironment. This discovery may lead to new treatments and diagnostic proceedings for colon cancer patients. A test to predict relapse cases and target treatments is likely to be ready in 5 years. This is particularly relevant as colon cancer is the second cause of cancer deaths worldwide. The study has been published by the prestigious journal Cancer Cell. It has been developed by a team of 17 researchers led by the Head of the lab Eduard Batlle and the associate researcher Elena Sancho.


The scientific community had been involved in a debate on the influence of the tumour\u2019s microenvironment on the surrounding healthy cells. The IRB study is the first scientific proof of the healthy cell\u2019s role regarding the metastasis of a specific tumour. The study has found that the presence of the TGF-beta molecule in the tumour\u2019s microenvironment (called stroma) makes the surrounding healthy cells segregate Interleukin-11 (IL-11). The IL-11 modifies the genetic programme of tumour cells and helps them to survive during the metastasis process, thus allowing them to travel and colonise other organs.

A test to predict relapse cases and target treatments, likely to be ready in 5 years

The study developed by a Barcelona-based team of scientists may have a direct impact on the development of new treatments for colon cancer, as well as improving its diagnosis and reducing the risk of metastasis. In about five years\u2019 time, a test might have been developed to predict relapse cases and adapt treatments according to the prognosis.

The Head of the IRB\u2019s Colorectal Cancer Laboratory, Eduard Batlle, and the Associate Researcher, Elena Sancho, presented the results on Monday, at the Barcelona BioMed Conference on \u2018Normal and Tumour Stem Cells\u2019. This conference was organised by IRB and the BBVA Foundation, and hosted at the Institut d\u2019Estudis Catalans (Catalonia\u2019s National Academy of Sciences).

\u201CThis study proposes a change in the paradigm\u201D, stated Batlle. \u201CUntil now, if we wanted to know whether a colon cancer patient was likely to develop metastasis, we would look at their tumour cells\u201D, he said. \u201CThis study has shown us that, instead of looking at the seed, we need to be looking at the earth. We can predict if a plant will grow if the ground, or substrate, in which the seed is planted is fertilized. TGF-beta is the fertilizer that changes the earth in which the tumour seed grows\u201D, he explained.

A study based on 345 cases

Research has been conducted on 345 cases of colon cancer, combining information from public databases and patient samples provided by 3 hospitals in Barcelona. The Catalan team identified the fundamental factors related to the metastasis process in colon cancers. The results showed that when tumour stem cells reach the patient\u2019s liver \u2013 which is a very usual target in this type of tumour\u2019s metastasis, they produce TGF-beta. This molecule is released into the microenvironment and the surrounding healthy cells (including macrophages, leukocytes, fibroblasts and endothelial cells) react by producing their own set of molecules. One of them is the IL11 protein, which is released into the tumour\u2019s microenvironment. Then, the IL11 has a direct effect on the tumour\u2019s stem cells, causing a series of genetic changes that help them to survive in other organs.

Furthermore, researchers found that tumour cells in the original organ can change their microenvironment. \u201CWe can tell whether there will be metastasis through indirect means. If we see that the stroma is already modified in the primary tumour site in the colon, it means that the tumour cells will also be able to change the microenvironment when they disseminate to the liver,\u201D said Alexandre Calon, a French postdoctoral fellow who is one of the authors of the study and is working in IRB\u2019s Colorectal Cancer lab.

Colon cancer has the second highest cancer mortality rate

This study is particularly relevant as colon cancer has the second highest cancer mortality rate worldwide, causing the second highest number of cancer deaths. The current treatment most of the time combines surgery and chemotherapy. However, between 30% to 40% of patients will relapse after several months or even a few years after the surgery. Most of these relapse cases involve metastasis, mainly to the liver or the lung. \u201CIn about five years, we will likely have a test on the market that identifies those patients at risk of metastasis, allowing doctors to fine tune their treatment regimes\u201D, stated Elena Sancho.

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  • A microscopy image of growing colon cancer cells surrounded by stroma cells (by E. Batlle lab, IRB, Alexandre Calon)

  • A microscopy image of growing colon cancer cells surrounded by stroma cells (by E. Batlle lab, IRB, Alexandre Calon)