The fatty regime promotes metastases of breast cancer in animal models

Obesity is associated with an increased risk of developing breast cancer and a greater probability for cancer to spread to other organs. But the causes of this association are still not well understood. Researchers from the National Spanish Cancer Research Center (CNIO) have now provided new data by discovering that a regime rich in active fat of the mechanisms that facilitate metastases.

This is a study led by Héctor Peinado, head of the CNIO microenvironment and metastase group, led in animal models of triple negative breast cancer that develop pulmonary metastases. It was published in Nature communications.

In order for cancer to spread to other organs, many tumor cells must leave the primary tumor, browse blood circulation, nest and proliferate in another organ. Sometimes the primary tumor sends molecules that modify the organ targets in advance, and prepares the equivalent of a nest that hosts tumor cells: it is the so-called “premetastatic niche”, in which the tumor cell can take root and develop metastases.

The CNIO group shows in its new study that the obese mice of eating too many big fat changes which promote the creation of the premetastatic niche, in this case in the lungs. More specifically, the activation of platelets and blood coagulation capacity are increased; In addition, fibronectin, the protein that connects pulmonary tissue cells, is activated.

A platelet armor

It is an established fact that obesity promotes blood coagulation, a process that depends on blood cells called platelets. Indeed, as Cnio’s researcher and the first author of the Marta Hergueta study observed, in animals fed with rich fats, the cells that are lost in the primary tumor are surrounded, during their trip through blood, by more platelets than in mice with normal diet.

One hypothesis is that the platelets could make it difficult for the defenses of the body to detect cancer cells: platelets would form “armor around tumor cells, preventing the immune system from recognizing and eliminating them”, explains Pinado.

Fertile reproduction group for metastases

In addition to affecting platelets, the CNIO group found that the regime rich in fat increases the expression of protein fibronectin in pulmonary tissue where tumor cells metastastize.

Fibronectin builds the tissue that connects pulmonary cells, thus facilitating the creation of the premetastatic niche that hosts the tumor cell. It also allows the tumor cell to interact more effectively with the platelets. “We have seen that the interaction of the tumor cell with the pulmonary endothelium and the brochure is regulated by fibronectin,” explains Peinado.

To study the implications of these results for human patients, the CNIO breast cancer clinical research unit, led by Miguel ángel Quintela, participated in the study.

After analyzing the blood samples of patients with triple negative breast cancer, obtained before surgery and after undergoing chemotherapy, it could not be verified that obesity posed an additional risk for the generation of metastases. However, patients with increased blood coagulation – with shorter prothrombin time – have proven to have a higher risk of relapse at five years.

These results “could help identify additional risk factors in patients with breast cancer undergoing treatment, thus contributing to better clinical management of the disease,” said Peinado.

Potential clinical application

The work, carried out in collaboration with other CNIO units and other centers in Spain and Canada, explored the initial routes for the clinical application of the results. One of them was to modify the diet in animal models. When the regime rich in fat has been removed and the mice lost weight, platelets and coagulation behavior returned to normal levels. As a result, metastases have been reduced.

“I think that these results, associated with clinical studies of other groups, have a future where food intervention or food changes, as well as control of platelet activity, can increase the efficiency of certain anti -tumor treatments,” explains Pinado. “They will not be treatments by themselves, but they can complete them.”