A team of 17 researchers, led by scientists Eduard Batlle and Elena Sancho in the Colorectal Cancer Laboratory at the Institute for Research in Biomedicine (IRB Barcelona), have determined that the ability of colon cancer to metastasize lies in the healthy cells, called stroma, that surround the tumour. Although the stroma has long been hypothesized to be complicit in this process, this study marks the first time that healthy cells in the microenvironment have been observed to play a fundamental role in allowing metastasis to occur in a specific tumour type.

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The discovery, which will be today’s Cancer Cell cover story, could translate into direct benefits for patients given that in a little more than five years, tests could be available to predict relapse allowing doctors to target treatment according to prognosis.

IRB Barcelona Group Leader Eduard Batlle, ICREA researcher and recipient of an ERC Starting Grant and the Banco Sabadell Biomedical Research Prize, and Associate Researcher Elena Sancho, presented their results at a press conference held during the Barcelona BioMed Conference on “Normal and Tumour Stem Cells”, organized by IRB Barcelona and the BBVA Foundation at the Institute d’Estudis Catalans.

Tumour stem cells corrupt healthy cells in tumour microenvironment

By studying 345 cases of colon cancer, using information in public databases and samples of patients provided by three hospitals in Barcelona, the team was able to identify the factors key to colon cancer metastasis. They showed that when tumour stem cells reach the liver, a common target of colon cancer metastasis, they release a molecule called TGF-beta into the microenvironment. The surrounding cells, including macrophages, leukocytes, fibroblasts and endothelial cells, respond by releasing a different set of molecules. The researchers found that the cells in the tumour microenvironment produce interleukin-11 (IL11) and cause a series of genetic changes in the tumour stem cells that allow it to survive in the foreign organ.

“This study proposes a change in paradigm”, explains Batlle. “Until now, if we wanted to know whether a colon cancer patient was likely to develop metastasis, we would look at their tumour cells. This 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.”

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