Cells responsible for metastasis in colon cancer identified for the first time

Researchers at the Spanish Institute for Biomedical Research (IRB) in Barcelona identified the cells responsible for relapse in colon cancer and the recurrence of cancer in other organs after removal of the primary tumor.

The finding, which is published this Wednesday in the journal “Nature”, shows that early immunotherapy, prior to surgery, can eliminate these cells before they initiate metastasis and thus prevent relapses in the disease.

According to the researchers, led by the head of the group at the Ciber -Biomedical Network Research Center- on Cancer (Ciberonc), Eduard Batllethis work opens the way to developing new therapeutic approaches and diagnostic tools to slow down the progression of the disease and improve the prognosis of colon cancer, the third most common, with nearly 2 million new cases each year in the world.

Batlle recalled that most patients are diagnosed when the tumor is still located in the colon or rectum, that they are removed by surgery and that in many cases they are treated with chemotherapy to prevent relapses, but in between 20 and 35 % of cases the cancer reappears in other organs in the form of metastasis.

According to Batlle, metastasis is caused by residual tumor cells that remain hidden at the time of surgery, mainly in the liver or lung.

Until now, research in colorectal cancer has focused on understanding the primary disease, although in recent years there have also been advances in characterizing metastatic disease once it manifests, but it had not yet been possible to investigate this small population of tumor cells that it is widespread and invisible to the diagnostic techniques used in the clinic.

Now, Eduard Batlle’s team has identified for the first time hidden residual tumor cells in the liver and lung, and has characterized how they evolve until metastasis appears in these organs.

“Understanding and avoiding the phenomenon of relapses after surgery is an unresolved medical need. After years of researching colon cancer, we have taken a first step to prevent metastases in patients who present with localized disease”, Batlle explained.

To carry out their research, the scientists generated a new experimental model in mice to recreate the process followed by patients who suffer relapses, and developed a methodology that makes it possible to isolate a tiny fraction of disseminated tumor cells hidden in the body.

“Our model, very similar to the progression of the disease in patients, has allowed us to characterize the primary tumor and the dynamics of the residual disease. We have studied micro-metastases of three or four cells, medium-sized metastases and even larger ones, characterizing how each of them evolves during the progression of the disease”, explained IRB researcher Adrià Cañellas-Socias.

In the amalgamation of cell types that forms colon cancers, researchers have identified a population, which they have called HRCs -for its acronym in English (High Relapse Cells or Cells with a High Probability of Relapse)-.

These cells have little proliferative activity and do not contribute to the growth of the primary tumor, but they are able to detach from the cancer in the colon, migrate to the bloodstream, reach the liver and remain hidden for a time after surgery.

In samples from patients with colon cancer, researchers have confirmed the presence of these same cells after treatment and have confirmed that eliminating these cells with genetic techniques is sufficient to prevent the formation of metastases.

Batlle’s team also developed a therapeutic strategy to specifically eradicate residual disease and prevent recurrence through immunotherapy treatment prior to surgery.

“Our discovery reveals for the first time how the group of tumor cells responsible for relapse behaves, and also the genes that define them. In addition, it represents a proof of concept that opens avenues for the development of new therapies specifically aimed at eliminating residual disease and new diagnostic tools to identify those patients with a higher risk of relapse”, Batlle summed up.

The work, in which researchers from the University of Oxford (United Kingdom), the Katholieke Universiteit de Leuven (Belgium), the National Center for Genomic Analysis (CNAG-CRG) and the Institute of Bioengineering of Catalonia also collaborated, suggests that in many cases it would be advisable to apply immunotherapy before surgery.

The research received funding from the “La Caixa” Foundation, the Spanish Association Against Cancer, Cancer Research UK, the Ministry of Science and Innovation and the European Research Council, among others.